Cell centrifugation device and method, controller, and medium

Abstract

Provided in the present application are a cell centrifugation device and method, a controller, and a medium. The cell centrifugation device comprises a cup body, which is provided with a centrifugal space and a first channel, wherein the cup body has a rotary axis, and the cup body can rotate around the rotary axis; the first channel comprises a conveying channel arranged at the top of the cup body and a curved channel arranged on a side wall of the cup body; a first opening and a second opening are respectively formed at two ends of the curved channel; the first opening is formed on an inner side wall of the cup body; the curved channel is in communication with the centrifugal space by means of the first opening, and the curved channel is in communication with the conveying channel by means of the second opening; and the curved channel further comprises at least one bent channel located on an outer side of the inner side wall of the cup body. In the present application, by means of designing the curved channel and the conveying channel on the cup body, the minimum concentration volume is reduced, the cost is reduced, and the cell centrifugation efficiency is improved.

Description

Cytocentrifugation device, method, controller and medium

[0001] This application claims priority to the Chinese patent application filed with the China Patent Office on September 22, 2023, with application number 202311240847.2, and invention name “Cell Centrifugation Device, Method, Controller and Medium”, the entire contents of which are incorporated by reference into this application. Technical Field

[0002] The present application belongs to the field of cell centrifugation technology, and in particular relates to a cell centrifugation device, method, controller and medium. Background Art

[0003] Currently, when performing cell separation, it is often necessary to use a cylindrical centrifuge device to perform cell centrifugation operations, utilizing the principle that the centrifugal force increases radially in a circular shape to separate the different components in the cell fluid. However, the inventors have realized that when centrifuging target cells, the centrifuge devices in the prior art generally have a large residual volume when extracting impurities and culture medium other than the target cells. This results in a large minimum concentrated volume that cannot meet the requirements of pharmaceutical companies. This requires connecting different devices to perform multiple centrifugation operations to meet the requirements, resulting in low efficiency and high costs. At the same time, the centrifuge devices in the prior art also have problems such as slow processing speed and long processing time. This also leads to low processing efficiency and increased costs.

[0004] Application Contents

[0005] The present application addresses technical problems in the prior art such as large residual volume and low efficiency during centrifugal operation of cell centrifuge devices, and provides a cell centrifuge device, method, controller and medium.

[0006] In view of the above technical problems, an embodiment of the present application provides a cell centrifuge device, comprising a cup body provided with a centrifugal space and a first channel; the cup body has a rotation axis, and the cup body can rotate around the rotation axis;

[0007] The first channel includes a conveying channel arranged at the top of the cup body, and a curve arranged on the side wall of the cup body; a first opening and a second opening are respectively provided at both ends of the curve; the first opening is arranged on the inner wall of the cup body; the curve is connected to the centrifugal space through the first opening, and the curve is connected to the conveying channel through the second opening; the curve also includes at least one bent channel located outside the inner wall of the cup body.

[0008] A cell centrifugation method, performed by the cell centrifugation device, comprising:

[0009] Controlling a first preset dose of separation fluid to flow into the centrifugal space within the cup body of the cell centrifuge device;

[0010] After controlling the cup body to rotate around the rotation axis at a first preset speed, controlling a second preset dose of sample liquid to flow into the centrifugal space at a preset flow rate;

[0011] Controlling the cup body to rotate at a second preset speed for a first preset time to centrifuge the liquid in the centrifugal space in the cup body, so that the target cells in the sample liquid are closely attached to the inner wall of the cup body;

[0012] After the centrifugal operation, the liquid except the target cells is discharged from the centrifugal space through the first opening of the first channel, the bend and the transport channel in sequence.

[0013] Optionally, after controlling the second preset dose of sample liquid to flow into the centrifugal space at a preset flow rate, the method further comprises:

[0014] A third preset dose of separation liquid is controlled to flow into the centrifugal space.

[0015] Optionally, the cup body further comprises a second channel, which is provided at the bottom of the cup body and communicates with the centrifugal space; after the liquid except the target cells after the centrifugal operation is discharged from the centrifugal space sequentially through the first opening, the bend, and the delivery channel, the method further comprises:

[0016] When it is detected that the liquid discharged from the first channel has been exhausted, controlling the target base liquid to flow into the centrifugal space;

[0017] controlling the cup body to rotate at a third preset speed for a second preset time to uniformly mix the target cells in the centrifugal space with the target base liquid to obtain a mixed liquid;

[0018] The mixed liquid in the centrifugal space is discharged into a preset storage container through the second channel.

[0019] A controller comprises a processor and a memory, wherein the memory stores an executable program, and the processor is configured to execute the executable program to implement the cell centrifugation method.

[0020] One or more readable storage media storing computer-readable instructions, wherein when the computer-readable instructions are executed by one or more processors, the one or more processors are caused to implement the cell centrifugation method according to any one of claims 12 to 14.

[0021] The cell centrifuge device provided in the present application includes a cup body provided with a centrifugal space and a first channel; the cup body has a rotation axis, and the cup body can rotate around the rotation axis; the first channel includes a delivery channel provided at the top of the cup body, and a bend provided on the side wall of the cup body; a first opening and a second opening are provided at each end of the bend; the first opening is provided on the inner side wall of the cup body; the bend is connected to the centrifugal space through the first opening, and the bend is connected to the delivery channel through the second opening; the bend also includes at least one bent channel located on the outer side of the inner side wall of the cup body. By designing the bend and the delivery channel on the cup body, the present application can maximize the extraction of other liquids except the target cells attached to the inner side wall of the cup body while minimizing the extraction of target cells, thereby minimizing liquid residue, reducing the minimum concentration volume, reducing costs, and improving cell centrifugation efficiency.

[0022] The details of one or more embodiments of the disclosure are set forth in the accompanying drawings and the description below, and other features and advantages of the disclosure will be apparent from the description, the drawings, and the claims. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] The present application is further described below with reference to the accompanying drawings and examples.

[0024] FIG1 is a schematic structural diagram of a cell centrifugation device provided in one embodiment of the present application.

[0025] FIG2 is a schematic structural diagram of a cup cover provided in another embodiment of the present application.

[0026] FIG3 is a schematic structural diagram of a liquid pusher plate provided in an embodiment of the present application.

[0027] FIG4 is a schematic flow chart of a cell centrifugation method according to an embodiment of the present application.

[0028] FIG5 is a schematic flow chart of a cell centrifugation method provided in another embodiment of the present application.

[0029] FIG6 is a schematic flow chart of a cell centrifugation method provided in another embodiment of the present application.

[0030] The figure marks in the specification are as follows: 100, cup body; 110, centrifugal space; 120, first channel; 121, conveying channel; 122, bend; 1221, first opening; 1222, second opening; 1223, bending channel; 130, groove; 140, conveying groove; 150, winding groove; 160, second channel; 161, third opening; 171, straight wall section; 172, slope section; 180, cup body; 190, cup cover; 191, first inlet and outlet channel; 192, second inlet and outlet channel; 200, liquid pushing plate; 210, liquid pushing body; 220, guide part; 211, connecting part; 212, pushing part. DETAILED DESCRIPTION

[0031] In order to make the technical problems, technical solutions and beneficial effects solved by this application more clearly understood, this application is further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain this application and are not intended to limit this application.

[0032] It should be understood that the terms "upper", "lower", "left", "right", "front", "back", "middle", etc., indicating the orientation or position relationship, are based on the orientation or position relationship shown in the accompanying drawings, and are only for the convenience of describing this application and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be understood as a limitation of this application.

[0033] As shown in Figures 1 to 3, an embodiment of the present application provides a cell centrifuge device, comprising a cup body 100 provided with a centrifugal space 110 and a first channel 120; the cup body 100 has a rotation axis, and the cup body 100 can rotate around the rotation axis; the first channel 120 includes a conveying channel 121 arranged at the top of the cup body 100, and a bend 122 arranged on the side wall of the cup body 100; a first opening 1221 and a second opening 1222 are respectively provided at both ends of the bend 122; the first opening 1221 is arranged on the inner wall of the cup body 100; the bend 122 is connected to the centrifugal space 110 through the first opening 1221, and the bend 122 is connected to the conveying channel 121 through the second opening 1222; the bend 122 also includes at least one bending channel 1223 located outside the inner wall of the cup body 100. 1 , the second opening 1222 is located substantially flush with the first opening 1221 (i.e., the inner sidewall of the cup body 100). However, in other embodiments, the second opening 1222 may be located on the outer side or the inner side of the inner sidewall of the cup body 100, and the invention is not limited thereto. The cup body 100 may be cylindrical or cylindrical.

[0034] Furthermore, the cell centrifuge device further comprises a rotation drive mechanism (not shown) connected to the cup body 100. The cup body 100 is driven by the rotation drive mechanism to rotate around the rotation axis to centrifuge the liquid contained in the centrifugal space.

[0035] In one embodiment, a first distance between the inflection point of the bending channel 1223 and the rotation axis is greater than a second distance between the inner sidewall of the cup body 100 and the rotation axis. The bending channel 122 may be composed of one or more sequentially connected bending channels 1223, and the inflection point refers to the point where each bending channel 1223 turns, including an outer inflection point and an inner inflection point. For example, in the embodiment shown in FIG1 , the inflection points include an outer inflection point located at the leftmost side of the bending channel 1223, and an inner inflection point located at a position corresponding to the outer inflection point (i.e., the rightmost point on the bending channel 1223 relative to the outer inflection point in FIG1 ). In this embodiment, within a preset height range of the bend 122 provided on the inner wall of the cup body 100, the distance between any point on the inner wall of the cup body 100 and the rotation axis is the second distance, and all second distances are smaller than the first distance between the inflection point of the bending channel 1223 and the rotation axis, so that the bending channel 1223 can always be located on the outside of the entire first opening 1222 away from the rotation axis (for example, only one bending channel 1223 is provided in Figure 1, and the bending channel 1223 is located on the outside of the first opening 1222 away from the rotation axis).

[0036] Furthermore, the bending channel 1223 includes, but is not limited to, a U-shaped bending channel or a J-shaped bending channel. In the cell centrifuge device shown in FIG1 , only one bending channel 1223 is provided. When the second opening 1222 is located near the inflection point, the bending channel 1223 is a J-shaped bending channel. When the second opening 1222 is located substantially flush with the first opening 1221 (i.e., the inner sidewall of the cup body 100), the bending channel 1223 is a U-shaped bending channel.

[0037] In this embodiment, the end of the delivery channel 121 away from the bend 122 is in communication with the outside world, allowing fluid (e.g., cell fluid, separation fluid, or gas) to be input into or output from the centrifugal space 110 of the cup body 100 through the delivery channel 121 and the bend 122. The inner sidewall of the cup body 100 refers to the side wall of the cup body 100 close to the rotation axis, i.e., the inner wall of the centrifugal space 110. The cup body 100 of the cell centrifuge device rotates about the rotation axis during the centrifugation process. Therefore, the target cells (target cells are generally relatively heavy) in the centrifugal space 110 adhere to the inner sidewall of the cup body 100 under the action of centrifugal force. The bending channel 1223 is located on the outside of the inner wall of the cup body 100, that is, the bending channel 1223 is bent in the direction away from the inner wall of the cup body 100, and the bending channel 1223 is located between the inner wall and the outer wall of the cup body 100; and the first opening 1221 is located on the inner wall. As shown in FIG1 , the bend 122 includes only one bending channel 1223, and the only bending channel 1223 is connected to the first opening 1221. In this way, when the liquid in the centrifugal space 110 is extracted through the first channel 120, the liquid will enter the bending channel 1223 from the first opening 1221. The curved channel 1223 is bent in a direction away from the inner wall of the cup body 100. Therefore, when the fluid enters the curved channel 1223 from the first opening 1221, the flow direction will be from the inner wall toward the outer wall of the cup body 100 (basically no or very little thrust from bottom to top will be generated). Therefore, during the entire process of extracting liquid through the first channel 120, since the target cells have been pressed and attached to the inner wall of the cup body 100 under the action of centrifugal force, and there is basically no thrust from bottom to top, extracting liquid through the first channel 120 will minimize the simultaneous extraction of target cells.

[0038] At the same time, when the liquid in the centrifugal space 110 is extracted through the first channel 120, since the cup 100 of the cytocentrifuge device rotates about the rotation axis during the centrifugation process, the liquid in the centrifugal space 110 other than the target cells will adhere to the inner sidewall of the cup 100 under the action of centrifugal force. Therefore, the first opening 1221 is located on the inner sidewall of the cup 100, which can maximize the extraction of liquid other than the target cells not adhering to the inner sidewall of the cup 100, thereby minimizing liquid residue. Compared to a top channel solution in which the channel opening is located at the top, when extracting liquid from the centrifugal space through the top channel, more liquid will inevitably remain at the end of the extraction (when the liquid is extracted close to the inner sidewall of the cup, some liquid will inevitably be unable to be extracted due to the presence of gas in the channel, or gas will be extracted along with the liquid).

[0039] In one embodiment, the first opening 1221 is disposed at the upper portion of the inner sidewall of the cup body 100. It is understood that the delivery channel 121 is disposed at the top of the cup body 100, and the curved channel 122 is connected to the delivery channel 121 via the second opening 1222. Therefore, disposing the first opening 1221 of the curved channel 122 at the upper portion of the inner sidewall of the cup body 100 allows the curved channel 122 to maintain a relatively short length, thereby reducing the amount of liquid remaining in the curved channel 122 and lowering the manufacturing cost of the curved channel 122. Furthermore, disposing the first opening 1221 at the upper portion of the inner sidewall of the cup body 100 can prevent some target cells from sliding down due to gravity, thereby preventing more target cells from flowing into the first opening 1211.

[0040] The cell centrifuge device provided in the present application includes a bend 122 arranged on the side wall of the cup body 100, the first opening 1221 of the bend 122 is arranged on the inner wall of the cup body 100, and the bending channel 1223 of the bend 122 is located on the outside of the inner wall of the cup body 100. Through the design of the bend 122 and the delivery channel 121 on the cup body 100, the present application can maximize the extraction of other liquids except the target cells attached to the inner wall of the cup body 100 while avoiding the extraction of target cells as much as possible, thereby minimizing the liquid residue, reducing the minimum concentration volume, reducing costs, and improving the cell centrifugation efficiency.

[0041] As shown in Figures 1 and 3, in some embodiments, the cytocentrifuge device further includes a push plate 200 mounted on the cup body 100 and positioned within the centrifugal space 110. When the cup body 100 rotates about the rotation axis, the push plate 200 rotates synchronously with the cup body 100, thereby pushing the liquid to rotate synchronously in the same direction as the cup body 100. It is understood that the push plate 200 rotates synchronously with the cup body 100 when the cup body 100 rotates, thereby reducing the relative motion between the outer layer of liquid near the inner sidewall of the cup body 100 and the inner layer of liquid near the rotation axis. The driving force for the rotation of the inner layer of liquid is no longer the viscous resistance between the outer and inner layers of liquid, but the thrust of the push plate 200. This prevents the shearing effect of the viscous resistance on the target cells in the liquid, thereby preventing shear damage to the target cells during the centrifugation process. It is understood that the specific number of push plates 2 can be 1, 2, 3, or 4, etc., and is not specifically limited herein.

[0042] As shown in Figures 1 to 3, in some embodiments, the top of the cup body 100 is provided with a conveying groove 140, and the side wall of the cup body 100 is provided with a winding groove 150 connected to the conveying groove 140; the liquid pushing plate 200 includes a liquid pushing body 210 and a guide portion 220 connected to the side of the liquid pushing body 210 away from the rotation axis; the top end of the liquid pushing body 210 is inserted into the conveying groove 140 and forms the conveying channel 121 with the groove wall of the conveying groove 140, and the bottom end of the liquid pushing body 210 is connected to the bottom surface of the cup body 100; the guide portion 220 is inserted into the winding groove 150 and forms the curved channel 122 with the winding groove 150. It is understood that the conveying channel 121 can be directly machined on the top of the cup body 100 or formed by combining multiple components; the curved channel 122 can be directly machined on the side wall of the cup body 100 or formed by combining multiple components. In this embodiment, to reduce manufacturing difficulty, the delivery channel 121 is formed by the top end of the liquid-pushing body 210 being inserted into the delivery groove 140 and enclosed by the groove wall of the delivery groove 140. The bend 122 is formed by the guide portion 220 being inserted into the recirculation groove 150 and enclosed by the recirculation groove 150. In this way, the liquid-pushing plate 210 is fully utilized, and the number of components is reduced while reducing manufacturing difficulty. Furthermore, when the guide portion 220 is inserted into the recirculation groove 150, the end of the guide portion 220 away from the rotation axis is located outside the inner side wall of the cup body 100, thereby allowing the first opening 1221 to be located on the inner side wall of the cup body 100.

[0043] As shown in Figures 1 to 3, in some embodiments, the liquid pushing body 210 includes a connecting portion 211 inserted into the conveying groove 140 and surrounding the conveying channel 121 with the groove wall of the conveying groove 140, and a pushing portion 212 connected to the bottom of the connecting portion 211, and the end of the pushing portion 212 away from the connecting portion 211 is connected to the bottom surface of the cup body 100; the guide portion 220 is connected to the connecting portion 211; a liquid gap connecting the first opening 1221 is provided between the pushing portion 212 and the inner side wall of the cup body 100; the distance between the side of the pushing portion 212 away from the liquid gap and the rotation axis is preset, and the preset distance is greater than the liquid gap.

[0044] In this embodiment, during the centrifugation of the cup body 100, the target cells in the sample liquid gradually approach the inner wall of the cup body 100 and pass through the liquid-passing gap, ultimately adhering to the inner wall of the cup body 100, thereby preventing the target cells from concentrating on the push plate 200. In addition, the sample liquid can freely pass through the liquid-passing gap, thereby ensuring that the liquid level on both sides of the push plate 200 remains consistent. Setting the preset distance between the push plate 200 and the rotation axis requires providing a certain amount of operating space for the installation and removal of the push plate 200. It is understandable that since the liquid-passing gap should not be set too large, the push plate 200 will not be able to achieve a good liquid-pushing effect if the liquid-passing gap is set too large. Since the linear velocity of the sample liquid near the rotation axis is relatively low during centrifugation, the spacing of the preset distance has a relatively small effect on the centrifugal effect of the sample liquid (and it requires a larger operating space). Therefore, the preset distance needs to be greater than the liquid-passing gap.

[0045] As shown in FIG. 1 , in some embodiments, the cup body 100 further includes a second channel 160 . The second channel 160 is disposed at the bottom of the cup body 100 and communicates with the centrifugal space 110 .

[0046] In this embodiment, the second channel 160 is arranged at the bottom of the cup body 100 and connected to the centrifugal space 110, so that liquid (such as sample liquid or separation liquid, etc.) can enter the centrifugal space 110 from the bottom of the cup body 100 through the second channel 160, thereby preventing splashing of the liquid when it is added to the centrifugal space 110 through the first channel 120, thereby ensuring the stability of the liquid during the process of adding it to the centrifugal space 110; in addition, after the sample liquid is centrifuged to obtain a mixed liquid, the mixed liquid can be gathered at the second channel 160 at the bottom of the cup body 100 under the action of gravity, thereby facilitating extraction through the second channel 160, thereby reducing the residual mixed liquid.

[0047] As shown in Figure 1, in some embodiments, the inner wall of the cup body 100 includes a straight wall section 171 and a slope section 172 connected to the bottom of the straight wall section 171, and the first opening 1221 is set on the straight wall section 171; the end of the slope section 172 away from the straight wall section 171 is connected to the bottom wall of the cup body 100; along the direction from top to bottom of the rotation axis, the vertical distance between the slope section 172 and the rotation axis gradually decreases. It can be understood that after the liquid other than the target cells is extracted through the first channel 120, the residual liquid (including the target cells) will remain on the chamfered position corresponding to the slope end 172 below the above-mentioned centrifugal space 110 after being mixed, thereby facilitating the maximum extraction of the residual liquid from the second channel 160; at the same time, in the process of extracting the liquid other than the target cells through the first channel 120, the liquid other than the target cells in the centrifugal space 110 can also overcome the influence of gravity under the action of centrifugal force, and the acceleration direction is toward the inner wall of the cup body 100. Therefore, the liquid in the slope section 172 will gather toward the straight wall section 171 under the action of centrifugal force. Therefore, the first opening 1221 is set on the straight wall section 171, which can extract the liquid other than the target cells that is not attached to the inner wall of the cup body 100 to the maximum extent, thereby minimizing liquid residue.

[0048] As shown in FIG1 , in some embodiments, the second channel 160 includes a third opening 161 disposed on the bottom wall of the cup body 100. The second channel 160 communicates with the centrifugal space 110 through the third opening 161. The end of the sloped section 172, distal from the straight-wall section 171, is disposed at the edge of the third opening 161. It will be appreciated that the third opening 161 can be disposed at a predetermined position on the bottom wall of the cup body 100 as desired. In this embodiment, the end of the sloped section 172, distal from the straight-wall section 171, is disposed at the edge of the third opening 161, meaning that the third opening 161 is located at the edge of the bottom wall of the cup body 100. This allows liquid to be better guided by the sloped section 172 to the third opening 161 when it is drawn through the second channel 160, further reducing residual liquid.

[0049] As shown in Figures 1 and 2, in some embodiments, the cup body 100 includes a cup body 180 with an opening at the top and a cup cover 190 that is detachable (the detachable method may include but is not limited to a snap connection, etc.) and covers the opening; the cup cover 190 is provided with a first inlet and outlet channel 191 and a second inlet and outlet channel 192 (it is understandable that the specific structural design of the first inlet and outlet channel 191 and the second inlet and outlet channel 192 is not limited to that shown in Figure 1, but the flow channel can be specifically designed according to needs, for example, the first inlet and outlet channel 191 can be provided with a first inlet and outlet channel 192. Different control valves are designed on the first and second inlet and outlet channels 191, 192 to control the flow passages. Pistons or the like can be installed at the locations where the first and second inlet and outlet channels 191, 192 connect to the cup body 100 or other components to facilitate sealing or flow direction changes, which will not be described in detail here. The first inlet and outlet channel 191 communicates with the end of the delivery channel 121 away from the bend; the second inlet and outlet channel 192 communicates with the end of the second channel 160 away from the centrifugal space 110. The bend is provided on the cup cover 190 and / or the cup body 180. It can be understood that the end of the first inlet and outlet channel 191 away from the delivery channel 121 is connected to the outside world, and the end of the second inlet and outlet channel 192 away from the second channel 160 is connected to the outside world, thereby allowing fluid (e.g., cell fluid, separation fluid, or gas) to be injected into the centrifugal space 110 of the cup body 100 through the first inlet and outlet channel 191 and / or the second inlet and outlet channel 192. It can be understood that the cup body 100 of the cell centrifuge device is in a state of rotating around the rotation axis during the centrifugation process. Therefore, the delivery channel 121 is generally connected to the first inlet and outlet channel 191 at the rotation axis (will not be displaced when the cup body 100 rotates) through a rotation seal or other connection method, and the second channel 160 is generally connected to the second inlet and outlet channel 192 at the rotation axis (will not be displaced when the cup body 100 rotates) through a rotation seal or other connection method, so that the first inlet and outlet channel 191 and the second inlet and outlet channel 192 are in a relatively static state during the rotation of the cup body 100, thereby facilitating communication with external pipelines. The curve can be set separately on the cup body 180, the curve can also be set separately on the cup cover 190, or the curve can be set on both the cup cover 190 and the cup body 180. The inner wall of the cup body 100 can include the inner wall of the cup cover 190 and / or the inner wall of the cup body 180; the curve is formed by the connection between the cup cover 190 and the cup body 180.

[0050] Furthermore, the cup cover 190 is provided with a vent hole (not shown) communicating with the centrifugal space. There is at least one vent hole, and a breathable membrane is disposed within the vent hole. Specifically, when the cell centrifuge is used for cell culture, the breathable membrane can prevent external bacteria from entering the centrifugal space. At the same time, the breathable membrane enables gas exchange between the centrifugal space and the outside world, ensuring normal respiration of the cells within the centrifugal space. Furthermore, the breathable membrane is preferably a hydrophobic breathable membrane.

[0051] In one embodiment, a groove 130 is defined on the inner wall of the cup body 100, and the first opening 1221 is disposed on the inner wall of the groove 130. It is understood that the target cells (which are generally relatively heavy) in the centrifugal space 110 adhere to the inner wall of the cup body 100 under the action of centrifugal force; when the liquid in the centrifugal space 110 is drawn into the inner wall of the cup body 100, some of the liquid may adhere to the inner wall of the cup body 100 due to the viscosity of the liquid. The groove 130 is provided on the inner wall of the cup body 100, that is, the groove 130 is provided in the direction of centrifugal force. Therefore, after the liquid in the centrifugal space 110 is drawn to the inner wall of the cup body 100, the liquid adhering to the inner wall of the cup body 100 will continue to accumulate in the groove 130. The first opening 1221 is provided on the inner wall of the groove 130, so that more of the liquid accumulated in the groove 130 can be drawn out through the first opening 1221 provided on the inner wall of the groove 130, thereby further reducing the minimum concentration volume. Furthermore, the first opening 1221 is provided on the inner wall of the groove 130 away from the rotation axis, thereby maximizing the extraction of liquid from the centrifugal space 110. The groove 130 can be configured as desired, for example, as a rectangular groove (gradient structure), a conical groove (continuous structure), or a spherical groove. The groove 130 can be provided on the lid and / or the cup body of the cup body.

[0052] As shown in FIG4 , an embodiment of the present application further provides a cell centrifugation method, which is performed by the cell centrifugation device, and includes:

[0053] S10: Controlling the flow of a first predetermined dose of separation fluid into the centrifugal space 110 within the cup 100 of the cytocentrifuge device. In one embodiment, by controlling the rotation of a peristaltic pump (which can be clockwise or counterclockwise, or can be another liquid pump) to cause the separation fluid to flow into the centrifugal space 110, the flow of the first predetermined dose of separation fluid into the centrifugal space 110 within the cup 100 of the cytocentrifuge device can be precisely controlled. The first predetermined dose of separation fluid can flow into the centrifugal space 110 within the cup 100 of the cytocentrifuge device through the first channel 120 (or the second channel 160). The first predetermined dose can be set based on actual conditions, as long as it provides a buffering effect on the sample fluid entering the centrifugal space 110 within the cup 100, for example, taking into account the length of the pipeline or the capacity of the centrifugal space 110 within the cup 100. In one embodiment, the first preset dose is 120 mL to 150 mL, ensuring that the separation fluid enters the centrifugal space 110 within the cup body 100 through the pipeline and acts as a buffer for the sample fluid entering the centrifugal space 110 within the cup body 100 in step S20. It is understood that in step S10, the cell centrifuge device may also be configured to start the cup body 100 rotating (the specific speed can be set as needed, for example, to the same as the first preset speed. In this case, the first preset speed can be maintained in step S20 without restarting the device) before injecting the separation fluid.

[0054] S20: After controlling the cup body 100 to rotate about the rotation axis at a first preset speed, a second preset dose of sample liquid is controlled to flow into the centrifugal space 110 at a preset flow rate. It is understood that controlling the cup body 100 to rotate about the rotation axis at the first preset speed also controls the cup body 100 to initiate the centrifugation operation. It is understood that controlling the cup body 100 to rotate about the rotation axis at the first preset speed can be performed before step S10, that is, controlling the cup body 100 to rotate about the rotation axis at the first preset speed and then controlling the first preset dose of separation liquid to flow into the centrifugal space 110 within the cup body 100 of the cell centrifuge device. Controlling the cup body 100 to rotate about the rotation axis at the first preset speed can also be performed after step S10, or simultaneously with step S10, thereby reducing processing time. The preset flow rate can range from 0 to 300 mL / min, and the preset flow rate can be achieved by squeezing the tubing through the rotation of a non-contact peristaltic pump. In this embodiment, the cup body 100 is first controlled to rotate about the rotation axis at a first preset speed, and then a second preset dose of sample liquid is controlled to flow into the centrifugal space 110 at a preset flow rate. This allows the sample liquid to be centrifuged immediately upon entering the centrifugal space 110, thereby reducing processing time and improving processing efficiency. The first preset speed can be set based on actual conditions to achieve optimal centrifugation effects for different sample liquid types. In one embodiment, the first preset speed is in the range of 2000-2500 rpm (Revolutions Per Minute), achieving optimal centrifugation effects for sample liquid containing PBMCs (the PBMCs in this sample liquid are the target cells). The second preset dose can be set based on actual conditions, generally taking into account factors such as the capacity of the sample liquid bag or the size of the centrifugal space 110. In one embodiment, the second preset dose is 150 mL-200 mL.

[0055] S30: Control the cup body 100 to rotate at a second preset speed for a first preset time to centrifuge the liquid in the centrifugal space 110 within the cup body 100, so that the target cells in the sample liquid adhere closely to the inner wall of the cup body 100. It will be appreciated that after the first preset dose of separation fluid and the second preset dose of sample liquid are injected into the centrifugal space 110, the liquid in the centrifugal space 110 can be continuously centrifuged. The first preset time can be set based on actual conditions to achieve optimal centrifugation for different sample liquid types or volumes. In one embodiment, the first preset time is 150 seconds, which achieves optimal centrifugation for a sample liquid volume of preferably 150 mL. The second preset speed can be set based on actual conditions (the second preset speed can be the same as or different from the first preset speed) to achieve optimal centrifugation for different sample liquid types. In one embodiment, the second preset speed is preferably 2000 rpm, which achieves optimal centrifugation for sample liquid containing PBMCs (target cells).

[0056] S40, the liquid except the target cells after the centrifugal operation is discharged from the centrifugal space 110 in sequence through the first opening 1221, the bend 122 and the delivery channel 121 of the first channel 120. It can be understood that the cup body 100 rotates continuously, and the target cells in the sample liquid (the target cells are generally relatively heavy, such as PBMC cells) are close to the inner wall of the cup body 100. The bending channel 1223 is located on the outer side of the inner wall of the cup body 100, that is, the bending channel 1223 bends in a direction away from the inner wall of the cup body 100, and the bending channel 1223 is located between the inner wall and the outer wall of the cup body 100; and the first opening 1221 is located on the inner wall. When the liquid in the centrifugal space 110 is extracted through the first channel 120, the liquid will enter the bending channel 1223 from the first opening 1221. 23. Because the curved channel 1223 bends away from the inner wall of the cup body 100, the fluid entering the curved channel 1223 from the first opening 1221 flows from the inner wall toward the outer wall of the cup body 100 (generating little or no downward thrust). Therefore, during the entire process of extracting liquid through the first channel 120, the target cells are already pressed against the inner wall of the cup body 100 by centrifugal force, and there is essentially no downward thrust. Therefore, extracting liquid through the first channel 120 minimizes the simultaneous extraction of target cells. Furthermore, when extracting liquid from the centrifugal space 110 through the first channel 120, since the cup body 100 of the cytocentrifuge device rotates about the rotation axis during centrifugation, liquid in the centrifugal space 110 other than the target cells will also adhere to the inner wall of the cup body 100 under the action of centrifugal force. Therefore, the first opening 1221 is provided on the inner wall of the cup body 100 , and can extract the liquid other than the target cells that is not attached to the inner wall of the cup body 100 to the maximum extent, thereby minimizing liquid residue.

[0057] Therefore, in the above embodiment of the present application, by designing the bend 122 and the delivery channel 121 on the cup body 100, while avoiding the extraction of target cells as much as possible, other liquids except the target cells attached to the inner wall of the cup body 100 can be extracted to the maximum extent, thereby minimizing the liquid residue, reducing the minimum concentration volume, reducing costs, and improving cell centrifugation efficiency.

[0058] As shown in FIG5 , in some embodiments, after controlling the second preset dose of sample liquid to flow into the centrifugal space 110 at a preset flow rate in step S20 , the method further includes:

[0059] S50: Control a third preset dose of separation liquid to flow into the centrifugal space 110. It is understood that in step S20, some sample liquid may remain in the pipeline before entering the centrifugal space 110. To avoid waste of sample liquid, in this embodiment, by controlling the third preset dose of separation liquid to flow into the centrifugal space 110, the sample liquid remaining in the pipeline can be pushed into the centrifugal space 110. The third preset dose is set based on actual conditions; it is sufficient to push all the sample liquid remaining in the pipeline into the centrifugal space 110. In one embodiment, the third preset dose is 30 mL to 40 mL.

[0060] As shown in FIG6 , in some embodiments, the cup body 100 further includes a second channel 160, which is disposed at the bottom of the cup body 100 and communicates with the centrifugal space 110. Step S40, after the liquid other than the target cells is discharged from the centrifugal space 110 through the first opening 1221, the bend 122, and the delivery channel 121 after the centrifugation operation, further includes:

[0061] S60: When it is detected that the liquid discharged from the first channel 120 has been exhausted, control the target base liquid to flow into the centrifugal space 110. The target base liquid includes but is not limited to at least one of a cleaning liquid, a freezing liquid, or a culture medium.

[0062] S70, control the cup body 100 to rotate at a third preset speed for a second preset time to evenly mix the target cells in the centrifugal space 110 with the target base liquid to obtain a mixed liquid. It can be understood that the third preset speed can be set according to actual conditions, so as to achieve the best mixing effect according to different types of sample liquids. In one embodiment, the third preset speed is 2000 rpm, so as to achieve the best mixing effect for the sample liquid containing PBMC cells. The second preset time can be set according to actual conditions, so as to achieve the best mixing effect according to different types of sample liquids. In one embodiment, the second preset time is 210 seconds, so as to achieve the best mixing effect for the sample liquid containing PBMC cells.

[0063] S80: The mixed liquid in the centrifugal space 110 is discharged into a predetermined storage container through the second channel 160. It will be appreciated that in this step, the cup body 100 stops rotating, and the mixed liquid in the centrifugal space 110 falls to the bottom of the cup body 100 under the action of gravity. The second channel 160 is provided at the bottom of the cup body 100, which can maximize the extraction of the mixed liquid from the bottom of the cup body 100, thereby preventing residual mixed liquid and thus reducing cost.

[0064] It is understandable that the above-mentioned cell centrifugation method is not limited to that described in the above-mentioned embodiments. The specific configuration of the cell centrifugation method of the present application corresponds one-to-one with the above-mentioned cell centrifugation device, and will not be described in detail here.

[0065] An embodiment of the present application further provides a controller, which includes a processor and a memory, wherein the memory stores an executable program, and the processor is configured to execute the executable program to implement the cell centrifugation method.

[0066] The specific configuration of the controller of this application corresponds to the above-mentioned cytocentrifugation method and will not be further described here. Each module in the above-mentioned controller can be implemented in whole or in part through software, hardware, or a combination thereof. Each of the above-mentioned modules can be embedded in or independent of the controller in hardware form, or can be stored in the controller in software form, so that the controller can call and execute the corresponding operations of each of the above modules.

[0067] An embodiment of the present application further provides one or more readable storage media storing computer-readable instructions, wherein when the computer-readable instructions are executed by one or more processors, the one or more processors implement the above-mentioned cell centrifugation method.

[0068] Those skilled in the art will understand that all or part of the processes in the above-mentioned embodiment methods can be implemented by instructing related hardware through computer-readable instructions. The computer-readable instructions can be stored in a non-volatile readable storage medium or a volatile readable storage medium. When the computer-readable instructions are executed, they can include the processes of the embodiments of the above-mentioned methods. Among them, any reference to memory, storage, database or other media used in the embodiments provided in this application may include non-volatile and / or volatile memory. Non-volatile memory may include read-only memory (ROM), programmable ROM (PROM), electrically programmable ROM (EPROM), electrically erasable programmable ROM (EEPROM) or flash memory. Volatile memory may include random access memory (RAM) or external cache memory. By way of illustration and not limitation, RAM is available in many forms, such as static RAM (SRAM), dynamic RAM (DRAM), synchronous DRAM (SDRAM), double data rate SDRAM (DDRSDRAM), enhanced SDRAM (ESDRAM), Synchronous Link DRAM (SLDRAM), Rambus direct RAM (RDRAM), direct memory bus dynamic RAM (DRDRAM), and memory bus dynamic RAM (RDRAM), etc.

[0069] Those skilled in the art will clearly understand that for the sake of convenience and brevity in description, only the division of the above-mentioned functional units and modules is used as an example. In actual applications, the above-mentioned functions can be distributed and completed by different functional units and modules as needed, that is, the internal structure of the system can be divided into different functional units or modules to complete all or part of the functions described above.

[0070] The above are merely examples of the cell centrifugation device, method, controller and medium of the present application and are not intended to limit the present application. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present application shall be included in the scope of protection of the present application.

Claims

1. A cell centrifuge device, wherein: The invention comprises a cup body provided with a centrifugal space and a first channel; the cup body has a rotation axis, and the cup body can rotate around the rotation axis; The first channel includes a conveying channel arranged at the top of the cup body, and a bend arranged on the side wall of the cup body; a first opening and a second opening are respectively provided at both ends of the bend; the first opening is arranged on the inner wall of the cup body; the bend is connected to the centrifugal space through the first opening, and the bend is connected to the conveying channel through the second opening; the bend also includes at least one bending channel located outside the inner wall of the cup body.

2. The cell centrifuge device according to claim 1, wherein A first distance between the inflection point of the bending channel and the rotation axis is greater than a second distance between the inner side wall of the cup body and the rotation axis.

3. The cytocentrifuge device according to claim 1, wherein The bending channel includes a U-shaped bending channel or a J-shaped bending channel.

4. The cell centrifuge device according to claim 1, wherein The cell centrifuge device also includes a liquid pushing plate installed on the cup body and located in the centrifugal space; When the cup body rotates around the rotation axis, the liquid pushing plate rotates synchronously with the cup body, thereby pushing the liquid to rotate synchronously in the same rotation direction as the cup body.

5. The cell centrifuge device according to claim 4, wherein: The top of the cup body is provided with a conveying groove, and the side wall of the cup body is provided with a winding groove connected to the conveying groove; The liquid pushing plate comprises a liquid pushing body and a flow guide portion connected to a side of the liquid pushing body away from the rotation axis; The top end of the liquid pushing body is inserted into the conveying groove and forms the conveying channel with the groove wall of the conveying groove, and the bottom end of the liquid pushing body is connected to the bottom surface of the cup body; the guide part is inserted into the winding groove and forms the bend with the winding groove.

6. The cell centrifuge device according to claim 5, wherein: The liquid pushing body includes a connecting part which is inserted into the conveying groove and forms the conveying channel with the groove wall of the conveying groove, and a pushing part connected below the connecting part, and the end of the pushing part away from the connecting part is connected to the bottom surface of the cup body; the guide part is connected to the connecting part; a liquid passing gap connected to the first opening is provided between the pushing part and the inner side wall of the cup body; a preset distance is set between the side of the pushing part away from the liquid passing gap and the rotation axis, and the preset distance is greater than the liquid passing gap.

7. The cytocentrifuge device according to any one of claims 1 to 6, wherein: The cup body further comprises a second channel, which is arranged at the bottom of the cup body and communicates with the centrifugal space.

8. The cytocentrifuge device according to claim 7, wherein: The inner side wall of the cup body comprises a straight wall section and a slope section connected below the straight wall section, the first opening is arranged on the straight wall section; one end of the slope section away from the straight wall section is connected to the bottom wall of the cup body; Along the direction from top to bottom of the rotation axis, the vertical distance between the slope section and the rotation axis gradually decreases.

9. The cytocentrifuge device according to claim 8, wherein: The second channel includes a third opening arranged on the bottom wall of the cup body; the second channel is connected to the centrifugal space through the third opening, and one end of the slope section away from the straight wall section is arranged at the opening edge of the third opening.

10. The cytocentrifuge device according to claim 7, wherein: The cup body comprises a cup body with an opening at the top and a cup cover detachably covering the opening; the cup cover is provided with a first access channel and a second access channel; The first inlet and outlet channel is connected to an end of the conveying channel away from the bend; the second inlet and outlet channel is connected to an end of the second channel away from the centrifugal space; and the bend is arranged on the cup cover and / or the cup body.

11. The cytocentrifuge device according to claim 1, wherein: A groove is provided on the inner side wall of the cup body, and the first opening is arranged on the inner wall of the groove.

12. A cell centrifugation method, wherein: The cell centrifugation method is performed by a cell centrifugation device according to any one of claims 1 to 11, and the cell centrifugation method comprises: Controlling a first preset dose of separation liquid to flow into the centrifugal space in the cup body of the cell centrifuge device; After controlling the cup body to rotate around the rotation axis at a first preset speed, controlling a second preset dose of sample liquid to flow into the centrifugal space at a preset flow rate; Controlling the cup body to rotate at a second preset speed for a first preset time to centrifuge the liquid in the centrifugal space in the cup body, so that the target cells in the sample liquid are closely attached to the inner wall of the cup body; After the centrifugal operation, the liquid except the target cells is discharged from the centrifugal space through the first opening of the first channel, the bend and the transport channel in sequence.

13. The cell centrifugation method according to claim 12, wherein: After controlling the second preset dose of sample liquid to flow into the centrifugal space at a preset flow rate, the method further includes: A third preset dose of separation liquid is controlled to flow into the centrifugal space.

14. The cell centrifugation method according to claim 12, wherein: The cup body further comprises a second channel, which is arranged at the bottom of the cup body and communicates with the centrifugal space; After the liquid except the target cells after the centrifugal operation is discharged from the centrifugal space through the first opening, the bend and the delivery channel in sequence, the method further comprises: When it is detected that the liquid discharged from the first channel has been exhausted, controlling the target base liquid to flow into the centrifugal space; Controlling the cup body to rotate at a third preset speed for a second preset time to evenly mix the target cells in the centrifugal space with the target base liquid to obtain a mixed liquid; The mixed liquid in the centrifugal space is discharged into a preset storage container through the second channel.

15. A controller, wherein: The controller comprises a processor and a memory, wherein the memory stores an executable program, and the processor is configured to execute the executable program to implement the cell centrifugation method according to any one of claims 12 to 14.

16. One or more computer-readable storage media storing computer-readable instructions, wherein: When the computer readable instructions are executed by one or more processors, the one or more processors are caused to implement the cell centrifugation method according to any one of claims 12 to 14.

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