Cell concentration method and device

Abstract

The invention provides a cell concentration method and device. The device comprises a driving unit, a horizontally-arranged rotating plate, a hose penetrating through the rotating plate, a pipe body connected with the hose and a conveying assembly composed of a feeding pipe, a discharging pipe, a feeding valve and a discharging valve. And the control unit realizes continuous centrifugal concentration of liquid containing cells by coordinating the rotating speed of the driving unit and the working modes of the feeding valve and the discharging valve. The hose keeps an internal flow channel unobstructed through the anti-distortion characteristic of the hose in the rotating process, the hose body tends to be in a horizontal state along with rotation of the rotating plate to form a stable centrifugal field, and the conveying assembly achieves continuous separation and recovery of cell sediment through multi-mode flow speed regulation and control. According to the technical scheme, through the anti-twisting property of the hose and the combined structure of the horizontal pipe body, the device structure is simplified, and the manufacturing cost is reduced.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of cell concentration and separation, in particular to a cell concentration method and device. BACKGROUND

[0002] In the field of biological medicine, cell culture, etc., cell concentration is a key step. The traditional centrifugal concentration method usually adopts intermittent operation, which needs to stop feeding and discharging for centrifugation, and the efficiency is low, and it is difficult to realize continuous processing of cells. Although the existing continuous flow centrifugation technology can realize continuous operation, the device structure is complex, the cost is high, and damage may be caused to some cells sensitive to shear force. SUMMARY

[0003] In view of the above problems, the present application provides a cell concentration method and device, which solves the problems of complex and high cost of existing continuous flow centrifugation devices.

[0004] To achieve the above purpose, in a first aspect, the present application provides a cell concentration method suitable for a cell concentration device, the cell concentration device comprising a tube and a conveying assembly, the tube being arranged at one end of a hose extending downward, the tube being airtight connected with the end of the hose, the tube being used for containing liquid containing cells to be concentrated; the conveying assembly comprising a feeding pipe and a discharging pipe, the feeding pipe and the discharging pipe being arranged in the hose, one end of the feeding pipe protruding into the tube, one end of the discharging pipe protruding into the tube;

[0005] The method comprises:

[0006] The soft tube is driven to rotate to generate anti-torsion deformation and drive the tube containing liquid to rotate, and the soft tube maintains the internal flow passage unobstructed through its own anti-torsion force during rotation;

[0007] The first pump-in mode is opened: the feeding pipe continuously transports the liquid containing cells to the bottom of the tube at a first preset flow rate;

[0008] The first pump-out mode is opened at the same time: the discharging pipe discharges the liquid at the top of the tube at a second preset flow rate, forming a continuous centrifugal concentration process;

[0009] When the accumulation amount of cell sediments at the bottom of the tube reaches a preset condition, the second pump-in mode is switched to;

[0010] The discharging pipe is adjusted to the second pump-out mode at the same time, discharging the liquid at the top of the tube in a preset incremental flow rate mode.

[0011] In some embodiments, the method comprises:

[0012] A first rotation speed threshold is set, and the rotating plate is driven to rotate, the soft tube generates anti-torsion deformation and drives the tube to rotate, comprising:

[0013] The control unit controls the driving unit to increase the rotation speed of the rotating plate to a first rotation speed threshold at a preset acceleration rate;

[0014] The state of the hose twist is monitored in real time during the acceleration process, and the driving torque of the driving unit is dynamically adjusted to maintain the hose within the allowable twist range, so that the pipe body tends to rotate horizontally;

[0015] When the rotation speed reaches a stable state, the control unit starts to inject the balancing liquid into the pipe body at a low speed, and determines the horizontal state by monitoring the hose deformation parameters and the spatial posture of the pipe body. The horizontal state determination conditions include that the hose twist fluctuation value is less than a preset twist threshold, the angle between the pipe body axis and the horizontal plane is less than a preset angle, and the pressure fluctuation of the feeding pipe is stable within a preset allowable range.

[0016] In some embodiments, the first pump-in mode is configured as continuous pump-in or intermittent pump-in; the first pump-out mode is configured as continuous pump-out or intermittent pump-out; the control unit synchronously opens the first pump-in mode of the feeding valve to control the feeding valve to continuously deliver the liquid containing cells to the bottom of the pipe body at a first preset flow rate, including:

[0017] The control unit dynamically adjusts the first preset flow rate according to the real-time rotation speed of the rotating plate, so that the feeding flow rate and the centrifugal force maintain a preset proportional relationship;

[0018] The pressure change of the feeding pipe is continuously monitored during the delivery process. When it is detected that the pressure fluctuation exceeds the allowable range, the control unit automatically adjusts the opening degree of the feeding valve to maintain stable delivery;

[0019] And, according to the change of the liquid level in the pipe body, the feeding flow rate is adjusted according to a preset algorithm to ensure that a stable feeding diffusion layer of the liquid containing cells is formed at the bottom of the pipe body;

[0020] The first pump-out mode of the discharging valve is opened to control the discharging valve to discharge the liquid at the top of the pipe body through the discharging pipe at a second preset flow rate, forming a continuous centrifugal concentration process. The first preset flow rate is greater than the second preset flow rate, including:

[0021] The control unit dynamically adjusts the second preset flow rate according to the real-time liquid level in the pipe body, so that the discharge rate of the liquid at the top of the pipe body and the feeding rate of the liquid containing cells maintain dynamic balance;

[0022] The pressure change of the discharging pipe is continuously monitored during the pump-out process. When an abnormal pressure fluctuation is detected, the control unit automatically adjusts the opening degree of the discharging valve to maintain stable discharge;

[0023] At the same time, based on the feedback of the solid-liquid interface position in the pipe body, the second preset flow rate is corrected in real time to ensure that the concentrated cell layer is maintained within a preset state fluctuation range and is not taken out.

[0024] In some embodiments, the second pump-in mode is configured as continuous pump-in or intermittent pump-in; the second pump-out mode is configured as continuous pump-out or intermittent pump-out; when the control unit detects that the cell sediment accumulation amount at the bottom of the tube body reaches a preset condition, switching the feed valve to the second pump-in mode comprises:

[0025] The control unit automatically adjusts the pulse frequency and single injection amount of the buffer injection according to the cell sediment accumulation amount, so that the flushing effect is uniformly distributed in the cell sediment;

[0026] Delaying a preset time after each pulse injection allows the buffer to fully penetrate, while monitoring the structural changes in the cell sediment, and dynamically adjusting the subsequent pulse parameters;

[0027] And at the same time, adjust the second pump-out mode of the discharge valve to discharge the liquid at the top of the tube body at an increasing flow rate, comprising:

[0028] The control unit sets the initial flow rate according to the rate of change of the cell sediment accumulation amount, and automatically increases the discharge flow rate when each accumulation amount reaches a decrease threshold;

[0029] After the discharge flow rate jumps, maintain stable discharge until the concentration of the liquid containing cells after detection drops to a preset critical value, and then enter the next flow rate adjustment period, ensuring that the liquid at the top of the tube body is continuously discharged while maintaining a constant target concentration.

[0030] In some embodiments, the method further comprises:

[0031] During the cell concentration process, the control unit injects auxiliary medium into a specific area in the tube body through the auxiliary pipe, comprising:

[0032] When an abnormal cell sediment accumulation amount is detected, the control auxiliary valve is controlled to inject density adjusting liquid in a pulse manner to improve the uniformity of the cell sediment;

[0033] Based on the real-time monitored solid-liquid interface position, a dynamic isolation layer is formed by injecting buffer through the auxiliary pipe to prevent cell resuspension;

[0034] After the concentration is completed, the control auxiliary valve is fully opened, and a cleaning liquid is injected into the tube body in the reverse direction through the auxiliary pipe to achieve efficient recovery of the cell sediment.

[0035] In some embodiments, the method further comprises:

[0036] The auxiliary pipe protrudes to the bottom of the tube body, and the port of the auxiliary pipe in the tube body is higher than the port of the feed pipe in the tube body;

[0037] When the control unit detects that the cell sediment accumulation amount at the bottom of the tube body reaches a preset condition:

[0038] adjusting the feed valve to a second pump-in mode to intermittently inject the buffer to flush the sediment layer, adjusting the auxiliary valve to a third pump-out mode to incrementally discharge the cell liquid from the cell sediment layer at an increasing flow rate, the third pump-out mode being configured as continuous or intermittent;

[0039] alternatively, adjusting the feed valve to a third pump-in mode to continuously inject the cell-containing liquid to be concentrated, the third pump-in mode being configured as continuous or intermittent, adjusting the auxiliary valve to a fourth pump-out mode to incrementally discharge the cell liquid from the cell sediment layer at an increasing flow rate, the fourth pump-out mode being configured as continuous or intermittent;

[0040] and adjusting the discharge valve to a second pump-out mode to discharge the liquid at the top of the tube body.

[0041] the driving unit is kept rotating at a constant speed until the concentrated cells are completely discharged, and the hose maintains the internal flow passage unobstructed by its own anti-twist force during rotation.

[0042] In a second aspect, the present application provides a cell concentration device suitable for the method of the first aspect, the device comprising a driving unit, a rotating plate, a hose, a tube body, a delivery assembly, and a control unit, the rotating plate being arranged at an output end of the driving unit, the rotating plate being horizontally arranged, the driving unit being configured to drive the rotating plate to rotate, the rotating plate being provided with at least one first through hole; the hose penetrating through the rotating plate from top to bottom through the first through hole, the number of the hose corresponding to the number of the first through hole; the tube body being arranged at an end of the hose extending downward, the tube body being airtight connected with the end of the hose, the tube body being configured to contain the cell liquid to be concentrated; the delivery assembly comprising a feed pipe, a discharge pipe, a feed valve, and a discharge valve, the feed pipe and the discharge pipe being arranged in the hose, one end of the feed pipe protruding into the tube body, one end of the discharge pipe protruding into the tube body, the feed valve being arranged on the feed pipe, the discharge valve being arranged on the discharge pipe; the control unit being electrically connected with the feed valve, the discharge valve, and the driving unit, the control unit being configured to control the rotating speed of the driving unit, and to control the pump-in mode of the feed valve and the pump-out mode of the discharge valve during the rotation of the rotating plate.

[0043] In some embodiments, the length of the feed pipe protruding into the tube body is different from the length of the discharge pipe protruding into the tube body.

[0044] In some embodiments, the delivery assembly further comprises an auxiliary pipe and an auxiliary valve; the auxiliary pipe being arranged in the hose, one end of the auxiliary pipe protruding into the tube body; the auxiliary valve being arranged on the auxiliary pipe, the auxiliary valve being electrically connected with the control unit.

[0045] In some embodiments, the length of the auxiliary pipe protruding into the tube body is different from the length of the discharge pipe protruding into the tube body; or, the length of the auxiliary pipe protruding into the tube body is different from the length of the feed pipe protruding into the tube body.

[0046] Differing from the prior art, in the technical solution, the cell concentration device comprises a driving unit, a rotating plate arranged horizontally, a hose penetrating through the rotating plate, a pipe body connected with the hose, and a conveying assembly composed of a feeding pipe, a discharging pipe, a feeding valve and a discharging valve. The control unit realizes continuous centrifugal concentration of the liquid containing cells by coordinating the rotating speed of the driving unit and the working modes of the feeding valve and the discharging valve. The hose maintains the internal flow passage unobstructed by its anti-twisting property during rotation, the pipe body tends to be horizontal with the rotating plate to form a stable centrifugal field, and the conveying assembly realizes continuous separation and recovery of cell precipitation by multi-mode flow rate regulation. The combination of the anti-twisting property of the hose and the horizontal pipe body simplifies the device structure and reduces the manufacturing cost. The differential control strategy of the feeding valve with a feeding flow rate greater than the discharging flow rate of the discharging valve, in combination with the intermittent buffer flushing and the stepwise discharging mode, not only realizes continuous processing, but also protects the cells sensitive to shear force. The structural design of the hose enables it to maintain the flow passage unobstructed during rotation, solving the problems of pipe winding and blockage commonly seen in traditional continuous flow centrifugal devices. The real-time monitoring of the control unit on the thickness of the centrifugal precipitation layer and the adaptive flow rate adjustment of the feeding valve and the discharging valve significantly improve the cell concentration efficiency and avoid the pollution risk caused by manual intervention.

[0047] The above invention content is only a summary of the technical solutions of the present application. In order for those skilled in the art to more clearly understand the technical solutions of the present application, and then can be implemented according to the content of the description and the drawings, and in order for the above-mentioned purposes and other purposes, features and advantages of the present application to be more easily understood, the following will be described in conjunction with the specific embodiments of the present application and the accompanying drawings. BRIEF DESCRIPTION OF DRAWINGS

[0048] The accompanying drawings are only used to illustrate the principles, implementation modes, applications, characteristics and effects of the specific embodiments and other related contents of the present application, and cannot be considered as limitations of the present application.

[0049] In the drawings:

[0050] Figure 1 The schematic diagram of the cell concentration device described in the specific embodiment;

[0051] Figure 2 The schematic diagram of the fixed frame described in the specific embodiment;

[0052] Figure 3 The first schematic diagram of the rotating plate described in the specific embodiment;

[0053] Figure 4 The second schematic diagram of the rotating plate described in the specific embodiment;

[0054] Figure 5Fig. 1 is a schematic view of the feeding pipe, discharging pipe and pipe body according to the embodiment;

[0055] Figure 6 Fig. 1 is a schematic view of the feeding pipe, discharging pipe, auxiliary pipe and pipe body according to the embodiment.

[0056] The reference signs involved in the above-mentioned figures are explained as follows:

[0057] 1. driving unit;

[0058] 2. rotating plate;

[0059] 21. first through hole;

[0060] 3. hose;

[0061] 4. pipe body;

[0062] 5. feeding pipe;

[0063] 6. discharging pipe;

[0064] 7. auxiliary pipe;

[0065] 8. fixing frame. DETAILED DESCRIPTION

[0066] To make the possible application scenarios, technical principles, implementable specific schemes, purposes and effects of the present application clear, the following will be described in detail in combination with the specific embodiments listed and the accompanying drawings. The embodiments described herein are only used to make the technical schemes of the present application clearer, thus only serve as examples, and cannot limit the protection scope of the present application.

[0067] In this text, the term “embodiment” means that the specific features, structures or characteristics described in combination with the embodiment can be contained in at least one embodiment of the present application. The term “embodiment” appearing at various positions in the specification does not necessarily refer to the same embodiment, and does not particularly limit the independence or association between other embodiments. In principle, in the present application, as long as there is no technical contradiction or conflict, the technical features mentioned in each embodiment can be combined in any way to form a corresponding implementable technical scheme.

[0068] Unless otherwise defined, the meanings of the technical terms used herein are the same as those commonly understood by the person skilled in the art to which the present application belongs; the use of related terms herein is only for the purpose of describing specific embodiments, and is not intended to limit the present application.

[0069] In the description of the present application, the phrase "and / or" is a description of a logical relationship between objects, which means that there can be three relationships, for example, A and / or B, which means that there are three cases: A exists, B exists, and A and B exist at the same time. In addition, the character " / " herein generally represents that the associated objects before and after are a "or" logical relationship.

[0070] In the present application, the terms such as "first" and "second" are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any actual quantity, primary and secondary or order relationship between the entities or operations.

[0071] In the present application, without more limitation, the "includes", "contains", "has" or other similar open expressions used in the sentence are intended to cover non-exclusive inclusion, and these expressions do not exclude the existence of other elements in the process, method or product including the described elements, so that the process, method or product including a series of elements can not only include those limited elements, but also include other elements not explicitly listed, or also include the elements inherent in such process, method or product.

[0072] As the same understanding as in the "Guidelines for Examination", in the present application, the expressions such as "greater than", "less than", "exceed" are understood as not including the number; the expressions such as "above", "below", "within" are understood as including the number. In addition, in the description of the embodiments of the present application, the meaning of "multiple" is more than two (including two), and similar expressions related to "multiple" are also understood in this way, for example, "multiple groups", "multiple times" and the like, unless otherwise explicitly limited.

[0073] In the description of the embodiments of the present application, the spatial-related expressions used, such as "center", "longitudinal", "transverse", "length", "width", "thickness", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "vertical", "top", "bottom", "inside", "outside", "clockwise", "counterclockwise", "axial", "radial", "circumferential", and the like, indicate the orientation or positional relationship based on the orientation or positional relationship shown in the specific embodiments or the drawings, and are only for the convenience of describing the specific embodiments of the present application or for the reader to understand, and do not indicate or imply that the indicated device or component must have a specific position, a specific orientation, or be constructed or operated in a specific orientation, and therefore cannot be understood as a limitation on the embodiments of the present application.

[0074] Unless otherwise defined, or limited by context, the terms used herein such as "mount", "connect", "connection", "fixed", "set", and the like, should be understood to be used in a broad sense. For example, "connection" can be fixed connection, or detachable connection, or integrated setting; it can be direct connection, or indirect connection through intermediate medium; it can be the relationship of two components combined together, or the relationship of interaction between two components, or the internal communication of two structures. For those skilled in the art to which the present application belongs, the specific meanings of the above terms in the embodiments of the present application can be understood according to the specific circumstances.

[0075] In the first aspect, the embodiment provides a cell concentration method suitable for a cell concentration device, the cell concentration device comprising a tube and a conveying assembly, the tube being arranged at one end of a hose extending downward, the tube being in airtight connection with the end of the hose, the tube being used for containing liquid containing cells to be concentrated; the conveying assembly comprising a feeding pipe and a discharging pipe, the feeding pipe and the discharging pipe being arranged in the hose, one end of the feeding pipe protruding into the tube, and one end of the discharging pipe protruding into the tube; the method comprising:

[0076] Driving the hose to rotate to generate anti-torsion deformation and drive the tube containing liquid to rotate, the hose maintaining the internal flow passage unobstructed through its own anti-torsion force during rotation;

[0077] Starting the first pump-in mode: the feeding pipe continuously transports the liquid containing cells to the bottom of the tube at a first preset flow rate;

[0078] Simultaneously starting the first pump-out mode, the discharging pipe discharges the liquid at the top of the tube at a second preset flow rate, forming a continuous centrifugal concentration process;

[0079] When the accumulation amount of cells at the bottom of the tube reaches the preset condition, switching the feeding valve to the second pump-in mode;

[0080] Simultaneously adjusting the discharging pipe to the second pump-out mode to discharge the liquid at the top of the tube at a preset incremental flow rate.

[0081] In the embodiment, when the rotating plate is driven to rotate, the hose resists the torsion stress through the elastic deformation of the material itself, and at the same time drives the tube to gradually reach a rotating state. By accurately controlling the initial rotating speed to ensure the stable start of the system, the anti-torsion characteristics of the hose avoid the sealing problem caused by the traditional rotary joint, and lay a foundation for continuous flow operation.

[0082] In this embodiment, the first pump-in mode refers to inputting the liquid containing cells into the tube at a constant flow rate. The first preset flow rate is set by considering the volume of the tube and the separation efficiency. The feed pipe directly delivers the liquid containing cells to the bottom of the tube, and the centrifugal force field is used to achieve rapid sedimentation. This ensures that fresh samples are always added from the sedimentation zone, avoiding the re-mixing of separated cells, and significantly improving the concentration efficiency.

[0083] In this embodiment, the first pump-in mode and the second pump-in mode can be the same or different, and this embodiment does not limit this. The cell sedimentation state includes: sediment layer thickness (optical / weight detection); sediment layer density (impedance / ultrasonic detection); interface clarity (image recognition). It should be noted that the preset parameters mentioned in this embodiment, such as preset conditions and preset proportional relationships, are understood as being able to be set by humans in advance.

[0084] In this embodiment, the first pump-in mode refers to inputting the liquid containing cells into the tube at a constant flow rate. The first preset flow rate is set by considering the volume of the tube and the separation efficiency. The feed pipe directly delivers the liquid containing cells to the bottom of the tube, and the centrifugal force field is used to achieve rapid sedimentation. This ensures that fresh samples are always added from the sedimentation zone, avoiding the re-mixing of separated cells, and significantly improving the concentration efficiency.

[0085] In this embodiment, the second pump-out mode is switched to a stepwise increasing flow rate strategy. As the cell sediment gradually loosens, the discharge rate can be gradually increased at a preset increasing flow rate, which can be a gradient type. The gradual discharge method ensures that the liquid at the top of the tube is uniformly discharged, avoiding the breakage of cell clumps caused by local turbulence, and maintaining the integrity of the cell population.

[0086] In this embodiment, the rotation is maintained until the discharge process is completed. The hose maintains the stability of the internal flow channel structure by relying on the material properties in the continuous rotation state. The entire operation process does not require shutdown or disassembly of parts, and the complete working cycle from feeding to concentration to discharge is achieved through programmed control.

[0087] This embodiment realizes automatic continuous flow cell concentration through the cooperative control of the hose and the conveying assembly. The anti-twist property of the hose solves the problem of rotary sealing, and the rotary architecture reduces the height of the device. Differential flow control ensures efficient separation, and the discharge process protects cell activity. The entire process is completed in a closed system, avoiding the risk of contamination, and is particularly suitable for the preparation of clinical-grade cell preparations.

[0088] In some embodiments, the method comprises:

[0089] A first rotation speed threshold is set, and the rotating plate is driven to rotate, the hose is deformed against torsion and drives the pipe body to rotate, comprising:

[0090] The control unit controls the driving unit to increase the rotation speed of the rotating plate to the first rotation speed threshold at a preset acceleration rate;

[0091] The hose torsion state is monitored in real time during the acceleration process, and the driving torque of the driving unit is dynamically adjusted to maintain the hose within the allowable torsion range, so that the pipe body tends to rotate horizontally;

[0092] When the rotation speed reaches a stable state, the control unit starts the feeding valve to inject the balancing liquid into the pipe body at a low speed, and determines the horizontal state by monitoring the hose deformation parameters and the pipe body space posture, and the horizontal state determination conditions include that the hose torsion fluctuation value is less than a preset torsion threshold, the pipe body axis and the horizontal plane included angle is less than a preset included angle, and the feeding pipe pressure fluctuation is stable within a preset allowable range.

[0093] In this embodiment, the first rotation speed threshold set by the starting control unit refers to the pre-set basic operation parameters of the driving unit. When the driving unit drives the rotating plate to rotate, the hose resists torsional stress through the elastic deformation of the material itself, and at the same time drives the pipe body to gradually reach a horizontal rotation state. By accurately controlling the initial rotation speed, the system is ensured to start smoothly, and the anti-torsion characteristics of the hose avoid the sealing problem caused by the traditional rotary joint, laying a foundation for continuous flow operation.

[0094] In this embodiment, the first pump-in mode of the feeding valve opened synchronously by the control unit refers to inputting the liquid containing cells into the pipe body at a constant flow rate, and the setting of the first preset flow rate needs to consider the pipe body capacity and separation efficiency. The feeding pipe directly delivers the liquid containing cells to the bottom of the pipe body, and uses the centrifugal force field to achieve rapid sedimentation. It ensures that fresh samples are always added from the sedimentation area, avoids the separated cells being stirred again, and significantly improves the concentration efficiency.

[0095] In this embodiment, the first pump-out mode of the discharge valve opened simultaneously refers to continuously discharging the liquid located at the top of the pipe body at a second preset flow rate lower than the feeding flow rate, and the flow rate difference forms a dynamic balance. The discharge pipe is located in the top area of the pipe body, and the accurately controlled liquid discharge rate at the top of the pipe body ensures the stable growth of the sediment layer. In this embodiment, when the cell sediment accumulation reaches a preset value, it switches to a buffer flushing stage, and the second pump-in mode of the feeding valve is changed to intermittent injection of buffer, which gently disturbs the sediment layer through pulse flow. It can effectively clean the sediment cells and prevent excessive shear from causing cell damage, and is particularly suitable for concentration operation of fragile cell types.

[0096] In this embodiment, the discharge valve switches to the second pumping mode using a stepped increasing flow rate strategy. As the sediment layer gradually loosens, the discharge rate is gradually increased according to a preset gradient. This gradual discharge method ensures that the liquid at the top of the pipe is discharged evenly, avoiding cell clumping breakage caused by local turbulence and maintaining the integrity of the cell population.

[0097] In this embodiment, the drive unit is kept rotating at a constant speed until the discharge process is completed. The hose maintains the stability of its internal flow channel structure by relying on its material properties while continuously rotating. The entire operation requires no machine shutdown or component disassembly, and a complete work cycle from feeding to concentration to discharge is achieved through programmed control.

[0098] In this embodiment, the control unit controls the drive unit to increase the rotational speed of the rotating plate to a first speed threshold at a preset acceleration rate. This means using a gradual acceleration method to avoid instantaneous torque impact. The preset acceleration rate is determined based on the material properties of the hose and the inertia of the entire hose body, ensuring smooth acceleration of the rotating plate. By optimizing the acceleration curve, irreversible deformation of the hose due to sudden force is prevented, while mechanical vibration during the start-up phase is reduced, creating conditions for subsequent precise separation.

[0099] In this embodiment, real-time monitoring of the hose's torsion state and dynamic adjustment of the drive torque refers to collecting parameters such as the hose's torsion angle and stress distribution through embedded sensors. The control unit dynamically adjusts the drive unit output based on the real-time data, ensuring that the hose remains within its elastic deformation range; closed-loop control guarantees torque transmission efficiency and avoids material fatigue damage.

[0100] In this embodiment, starting the feed valve to inject the balancing fluid at a low speed is a calibration operation before the system reaches steady-state operation. The balancing fluid is used to establish the initial fluid environment, and its injection rate is set to 10-20% of the normal operating flow rate. By simultaneously monitoring hose deformation parameters, pipe spatial orientation, and pipeline pressure fluctuations, a multi-dimensional horizontal state determination system is formed. The hose torsion fluctuation value reflects the torsional stress balance, the pipe axis angle characterizes the horizontality of the rotation plane, and the pressure fluctuation value indicates the flow channel patency.

[0101] This embodiment achieves smooth transition and precise calibration of the rotating system through an intelligent start-up control process. The combination of a preset acceleration curve and real-time torque adjustment ensures the hose remains within a safe deformation range, while an embedded monitoring system constructs a multi-dimensional condition assessment framework. Equilibrium fluid injection and a multi-parameter verification mechanism provide a stable fluid environment for subsequent separation operations.

[0102] In some embodiments, the first pumping mode is configured as continuous pumping or intermittent pumping; the first pumping mode is configured as continuous pumping or intermittent pumping; the control unit synchronously opens the first pumping mode of the feed valve, and controls the feed valve to continuously deliver cell-containing liquid to the bottom of the tube through the feed pipe at a first preset flow rate, including:

[0103] The control unit dynamically adjusts the first preset flow rate according to the real-time rotation speed of the rotating plate, so that the feed flow rate and centrifugal force maintain a preset proportional relationship.

[0104] During the conveying process, the pressure change in the feed pipe is continuously monitored. When the pressure fluctuation exceeds the allowable range, the control unit automatically adjusts the opening of the feed valve to maintain stable conveying.

[0105] In addition, the feed flow rate is adjusted according to the change in liquid level in the tube, based on a preset algorithm, to ensure that the liquid containing cells forms a stable feed diffusion layer at the bottom of the tube.

[0106] In the first pumping mode of opening the discharge valve, the liquid located at the top of the pipe is discharged through the discharge pipe at a second preset flow rate, forming a continuous centrifugal concentration process. The first preset flow rate is greater than the second preset flow rate, including:

[0107] The control unit dynamically adjusts the second preset flow rate according to the real-time liquid level in the tube, so that the liquid discharge rate at the top of the tube and the liquid feeding rate containing cells are kept in dynamic balance.

[0108] During the pumping process, the pressure change in the discharge pipe is continuously monitored. When abnormal pressure fluctuations are detected, the control unit automatically adjusts the opening of the discharge valve to maintain stable discharge.

[0109] Simultaneously, based on the feedback of the solid-liquid interface position within the tube, the second preset flow rate is corrected in real time to ensure that the concentrated cell layer is maintained within the preset fluctuation range and is not carried out.

[0110] In this embodiment, the control unit dynamically adjusts the first preset flow rate based on the rotation speed of the rotating plate, establishing a flow rate-centrifugal force linkage control mechanism. By matching the feed flow rate and centrifugal acceleration in real time, a stable laminar diffusion of the cell-containing liquid is ensured at the bottom of the tube. Closed-loop control of pressure monitoring and valve opening further ensures the stability of the conveying process and avoids disturbance to the sedimentation layer caused by pulsed feeding. The flow rate compensation algorithm based on liquid level feedback realizes feed control in three-dimensional space, and the resulting diffusion layer structure makes the cell distribution more uniform.

[0111] In this embodiment, the control unit dynamically adjusts the second preset flow rate based on the liquid level, constructing an adaptive discharge balancing system. By calculating the volume difference between the feed and discharge in real time, the working liquid level inside the tube is dynamically maintained stable. A rapid response mechanism for abnormal pressure fluctuations prevents pipe blockage or cavitation, while solid-liquid interface position feedback enables precise boundary control of the concentrate layer. This ensures that the liquid discharge process at the top of the tube maintains continuous flow characteristics, preventing accidental loss of concentrated cells.

[0112] This embodiment achieves precise control of the cell concentration process through an intelligent fluid control system. It overcomes the separation efficiency fluctuations caused by rotational speed changes in traditional fixed flow rate modes, ensuring that cell sedimentation remains in an optimal hydrodynamic environment. The stable diffusion layer structure formed by the dynamic compensation algorithm, combined with the precisely controlled discharge mode, jointly constructs a highly efficient and stable continuous flow separation environment.

[0113] In some embodiments, the second pumping mode is configured as continuous pumping or intermittent pumping; the second pumping mode is configured as continuous pumping or intermittent pumping; when the control unit detects that the accumulation of cell sediment at the bottom of the tube reaches a preset condition, switching the feed valve to the second pumping mode includes:

[0114] The control unit automatically adjusts the pulse frequency and single injection volume of the buffer solution based on the amount of cell sediment accumulation, so that the flushing effect is evenly distributed in the cell sediment.

[0115] After each pulse injection, a preset time is allowed to allow the buffer solution to fully infiltrate, while the structural changes in the cell sediment are monitored, and the parameters of subsequent pulses are dynamically adjusted.

[0116] And, simultaneously adjusting the second pumping mode of the discharge valve to discharge the liquid located at the top of the pipe in a stepped increasing flow rate mode, including:

[0117] The control unit sets the initial flow rate based on the rate of change of cell sediment accumulation, and automatically increases the discharge flow rate each time a threshold for decreasing accumulation is reached.

[0118] After the discharge flow rate jumps, it maintains a stable discharge until the concentration of the cell-containing liquid detected drops to a preset critical value, and then enters the next flow rate adjustment cycle to ensure that the liquid at the top of the tube maintains a constant target concentration during continuous discharge.

[0119] In this embodiment, the control unit automatically adjusts the pulse parameters of the buffer solution (if applicable) injection based on the amount of accumulated cell sediment, establishing an intelligent sediment cleaning mode. Dynamic matching of pulse frequency and single injection volume ensures uniform coverage of the sediment surface with buffer solution, avoiding insufficient rinsing or over-dilution in certain areas. The set delayed permeation time allows the buffer solution to fully wet the intercellular spaces, and combined with parameter adjustments achieved through real-time structural monitoring, forms a gradual and gentle cleaning process. The pulse-permeation-feedback cyclic operation mode effectively removes impurities while maximizing the preservation of the cell clump structure integrity.

[0120] In this embodiment, the control unit sets the flow rate strategy based on the rate of change in cell sediment accumulation, which can be a stepped increase or decrease in flow rate to construct a concentration-self-stabilizing discharge control system. The initial flow rate setting is directly related to the state of the cell sediment, and the flow rate jump mechanism triggered by the decrease in accumulation threshold achieves precise matching of discharge capacity. Concentration threshold detection ensures that the quality of the cell-containing liquid remains stable within each flow rate step, forming a collaborative working mode of pulse-type washing and stepped discharge.

[0121] This embodiment achieves continuous preparation of high-purity cell concentrates through intelligent buffer rinsing and step-by-step discharge control. Pulsed injection mode ensures gentle cleaning of the precipitate layer, while a delayed permeation mechanism guarantees effective impurity removal. Step-by-step flow rate adjustment triggered by the rate of accumulation maintains stable discharge concentration, and concentration threshold detection enables closed-loop control of discharge quality. This simultaneously improves the viability retention and impurity removal rate of the cell concentrates, and the continuous flow operation significantly enhances processing efficiency.

[0122] In some embodiments, the delivery assembly further includes an auxiliary pipe and an auxiliary valve. The auxiliary pipe is disposed inside the hose, with one end of the auxiliary pipe protruding into the hose body. The auxiliary valve is disposed on the auxiliary pipe and is electrically connected to the control unit.

[0123] In some embodiments, the method further includes:

[0124] During cell concentration, the control unit injects an auxiliary medium into a specific area within the tube via an auxiliary tube, including:

[0125] When an abnormal accumulation of cell sediment is detected, the auxiliary valve is controlled to inject density-adjusting fluid in a pulse manner to improve the uniformity of cell sediment.

[0126] Based on real-time monitoring of the solid-liquid interface position, a dynamic isolation layer is formed by injecting buffer solution through an auxiliary tube to prevent cell resuspension.

[0127] After concentration is complete, the auxiliary valve is fully opened, and the washing solution is injected back into the cell sediment through the auxiliary tube to achieve efficient recovery of the cell sediment.

[0128] In this embodiment, the control unit achieves dynamic regulation by injecting an auxiliary medium into the tube body through an auxiliary tube. When an abnormal accumulation of cell sediment is detected, the system controls the auxiliary valve to inject density-adjusting fluid in a pulsed manner. The pulse injection mode can automatically adjust the injection intensity according to the density distribution difference, allowing the adjusting fluid to accurately penetrate into areas of uneven density, thereby changing the physicochemical properties of the local microenvironment and promoting the redistribution of cell sediment. This embodiment avoids product loss caused by traditional bulk dilution and maintains the stability of the overall structure of the cell sediment.

[0129] In this embodiment, based on real-time monitoring of the solid-liquid interface position, the control unit injects buffer solution through an auxiliary tube to form a dynamic isolation layer. The injection position and flow rate of the buffer solution are adjusted in real time according to feedback from the interface sensor, forming a transition zone with a specific viscosity gradient at the solid-liquid interface. This isolation layer not only prevents precipitated cells from diffusing into the liquid at the top of the tube, but also maintains the effective transmission of centrifugal force, solving the cell resuspending problem caused by interface blurring during traditional centrifugation.

[0130] In this embodiment, after concentration is complete, the auxiliary valve is fully opened to achieve efficient recovery of cell sediment. The reverse-injected washing fluid impacts the sediment layer tangentially from the end of the auxiliary tube, and the resulting fluid shear force gently deagglomerates the cell clumps. This integrated recovery method avoids the localized turbulence and cell damage caused by traditional pipette extraction, while ensuring the complete transfer of cell sediment.

[0131] This embodiment achieves precise control of the auxiliary media required during centrifugation through auxiliary tubes. Pulsed density-adjusting fluid injection effectively improves the uniformity of cell sediment, the dynamic isolation layer significantly enhances the clarity of the separation interface, and the reverse washing mechanism greatly improves cell recovery efficiency. Most importantly, these three aspects are parallel; that is, the control method of the auxiliary tubes can be set according to actual needs, and even the number of auxiliary tubes can be set to meet different centrifugation requirements. This embodiment solves the problems of uneven density, blurred interface, and difficult recovery in traditional centrifugation processes while maintaining cell viability, facilitating precise process control in experiments.

[0132] In some embodiments, the method further includes:

[0133] The auxiliary tube extends to the bottom of the tube body, and the port of the auxiliary tube inside the tube body is higher than the port of the feed tube inside the tube body.

[0134] When the control unit detects that the accumulation of cell sediment at the bottom of the tube has reached a preset condition:

[0135] Adjust the feed valve to the second pumping mode to intermittently inject buffer solution to flush the precipitate layer. Adjust the auxiliary valve to the third pumping mode to discharge the cell fluid from the cell precipitate layer at an increasing flow rate. The third pumping mode can be configured as continuous pumping or intermittent pumping.

[0136] Alternatively, adjust the feed valve to the third pumping mode to continuously inject the liquid containing cells to be concentrated. The third pumping mode is configured as continuous or intermittent pumping. Adjust the auxiliary valve to the fourth pumping mode to discharge the cell fluid of the cell precipitate layer at an increasing flow rate. The fourth pumping mode is configured as continuous or intermittent pumping.

[0137] In addition, adjust the discharge valve to the second pumping mode to discharge the liquid located at the top of the pipe;

[0138] The drive unit is kept rotating at a constant speed until the concentrated cells are completely discharged. During the rotation, the hose maintains the smooth flow of the internal channels through its own anti-torsion force.

[0139] In this embodiment, the auxiliary tube is installed inside the flexible tube using a nested design. The port position of the auxiliary tube is precisely set, creating a height difference above the feed tube port. This structural layout allows the auxiliary tube to contact the sedimentation layer while avoiding interference with the main feed channel, providing a physical basis for multi-mode operation. The control unit coordinates the operation of the auxiliary valve and the feed valve to achieve intelligent switching between different operating modes.

[0140] Specifically, in this embodiment, when the cell sediment layer reaches a preset thickness, the control unit activates the buffer flushing mode. The feed valve switches to the second pumping mode to generate an intermittent buffer flow, and the auxiliary valve simultaneously activates the third pumping mode to discharge the liquid located at the top of the tube at a stepped flow rate. The stepped flow rate is automatically adjusted according to the compaction of the sediment layer. The initial low-speed stage ensures interface stability, and the subsequent flow rate increases to match the shear resistance of the cell sediment, achieving a gentle and efficient stratification process.

[0141] In this embodiment, the continuous feeding mode employs different valve combination strategies. The feed valve maintains the third pump-in mode to sustain the supply of cell sediment, while the auxiliary valve activates the fourth pump-out mode to perform stepped discharge. This mode achieves continuous production while maintaining the accumulation of cell sediment through a dynamic balance between flow rate and feed volume, making it particularly suitable for large-scale concentration operations.

[0142] In this embodiment, the discharge valve always maintains the second pumping mode in coordination with other valve operations. Its stepped flow velocity curve is precisely coupled with the centrifuge speed, with each flow velocity step corresponding to a specific centrifugal force parameter, ensuring that the liquid at the top of the tube maintains a stable solid-liquid separation state during discharge. The torsion resistance of the hose material overcomes the problem of flow channel deformation during rotation.

[0143] This embodiment achieves an intelligent upgrade of the centrifugal concentration process through multi-valve linkage control. The three-dimensional layout of the auxiliary tube and feed tube creates a collaborative working space, the buffer flushing mode improves the purity of cell sediment, the continuous feed mode ensures processing efficiency, and the step-by-step discharge mechanism maintains stable product concentration. The flow channel maintenance technology in the rotating state solves the dynamic sealing problem. This embodiment completes the entire process from concentration to discharge in a closed environment, significantly improving the recovery rate and activity retention rate of cell products.

[0144] Please see Figures 1 to 5In a second aspect, this embodiment provides a cell concentration device suitable for the method described in the first aspect. The device includes a drive unit 1, a rotating plate 2, a flexible tube 3, a tube body 4, a delivery assembly, and a control unit. The rotating plate 2 is disposed at the output end of the drive unit 1 and is arranged horizontally. The drive unit 1 drives the rotating plate 2 to rotate. The rotating plate 2 has at least one first through hole 21. The flexible tube 3 passes through the first through hole 21 from top to bottom through the rotating plate 2, and the number of flexible tubes 3 corresponds to the number of first through holes 21. The tube body 4 is disposed at the downward extending end of the flexible tube 3. The end of the hose 3 is airtightly connected, and the tube body 4 is used to hold the cell fluid to be concentrated; the delivery assembly includes an inlet pipe 5, an outlet pipe 6, an inlet valve, and an outlet valve. The inlet pipe 5 and the outlet pipe 6 are both installed inside the hose 3. One end of the inlet pipe 5 protrudes into the tube body 4, and one end of the outlet pipe 6 protrudes into the tube body 4. The inlet pipe 5 is equipped with an inlet valve, and the outlet pipe 6 is equipped with an outlet valve; the control unit is electrically connected to the inlet valve, the outlet valve, and the drive unit 1. The control unit is used to control the rotation speed of the drive unit 1 and to control the pumping mode of the inlet valve and the pumping mode of the outlet valve during the rotation of the rotating plate 2.

[0145] In this embodiment, the drive unit 1 preferably uses a servo motor to ensure precise and controllable rotation speed. The rotating plate 2 is a horizontally arranged rigid structure, which can be made of stainless steel or aluminum alloy, or polyurethane or biomaterials as needed. The conveying assembly includes an inlet pipe 5, an outlet pipe 6, and inlet and outlet valves. Both the inlet pipe 5 and the outlet pipe 6 are housed within the flexible tube 3. One end of the inlet pipe 5 protrudes into the tube body 4, and one end of the outlet pipe 6 protrudes into the tube body 4. The inlet pipe 5 is equipped with an inlet valve, and the outlet pipe 6 is equipped with an outlet valve. The control unit is electrically connected to the inlet valve, the outlet valve, and the drive unit 1, and is used to coordinate and control the rotation speed of the drive unit 1 and the operating modes of the inlet and outlet valves. The inlet and outlet valves preferably use peristaltic pumps to avoid shearing damage to the cells.

[0146] The flexible tubing 3 is made of medical-grade silicone, PTFE with reinforcing fibers, or medical-grade PVC, capable of withstanding torsional torque and maintaining unobstructed flow. The bottom of the tubing 4 is preferably tapered to promote cell sedimentation and aggregation. The end opening of the feed tube 5 should be close to the inner wall of the bottom of the tube, while the inlet end of the discharge tube 6 is preferably designed with a beveled opening to enhance the liquid collection efficiency at the top of the tube.

[0147] In this embodiment, the drive unit 1 drives the horizontal rotating plate 2 to rotate, causing the hose 3 and tube body 4 passing through it to rotate synchronously, generating a centrifugal force field. Liquid containing cells is continuously fed into the bottom of tube body 4 via the feed pipe 5, controlled by the feed valve. Under centrifugal force, a concentrated layer is formed, while the liquid at the top of the tube body is discharged through the discharge pipe 6, regulated by the discharge valve. This achieves true continuous flow operation. The horizontally rotating plate 2 and hose 3 simplify the equipment structure, the flexible tubing ensures cell viability, and the multi-valve independent control mode allows for precise adjustment of the concentration ratio.

[0148] Please see Figure 5 In some embodiments, the length of the feed pipe 5 extending into the tube body 4 differs from the length of the discharge pipe 6 extending into the tube body 4. The distance between the end of the feed pipe 5 and the bottom of the tube body 4 ensures that the feed inlet is close to the sedimentation zone but does not contact the sediment at the bottom of the tube, while the distance between the ends of the discharge pipe 6 ensures that its opening is always located in the liquid layer at the top of the tube body. This embodiment creates spatial separation between the feed zone and the discharge zone through the differentiated lengths, allowing the cell-containing liquid to be concentrated to enter efficiently from the bottom and the liquid at the top of the tube body to be discharged stably from the top.

[0149] Please see Figure 6 In some embodiments, the delivery assembly further includes an auxiliary pipe 7 and an auxiliary valve; the auxiliary pipe 7 is disposed within the flexible tube 3, with one end protruding into the tube body 4; the auxiliary valve is disposed on the auxiliary pipe 7 and is electrically connected to the control unit. The extended end of the auxiliary pipe 7 differs in length from the inlet pipe 5 and the outlet pipe 6, preferably located in the intermediate layer region between them, enabling functions such as buffer replenishment, intermediate component discharge, or online monitoring. The auxiliary valve, as an independent fluid control unit, can adjust the operating mode of the auxiliary pipe 7 according to process requirements.

[0150] Please see Figure 6In some embodiments, the length of the auxiliary tube 7 protruding into the tube body 4 is different from the length of the outlet tube 6 protruding into the tube body 4; or, the length of the auxiliary tube 7 protruding into the tube body 4 is different from the length of the inlet tube 5 protruding into the tube body 4. The extended end of the auxiliary tube 7 protrudes into the tube body 4 at a specific length, which can be adjusted according to actual process requirements. Specifically: when used as a buffer replenishment channel, the length of the auxiliary tube 7 can be similar to the length of the inlet tube 5; when used for intermediate component discharge, the length of the auxiliary tube 7 can be set to an intermediate value between the lengths of the inlet tube 5 and the outlet tube 6; when used as a monitoring channel, the length of the auxiliary tube 7 can be set independently to meet detection requirements. The variable length configuration allows the auxiliary tube 7 to flexibly perform multiple functions, including but not limited to: replenishing reagents as a secondary feed channel, connecting sensors as a monitoring channel, or selectively discharging intermediate components as an auxiliary discharge channel. Through precise control of the auxiliary valve by the control unit, the coordinated operation of the inlet tube 5, the outlet tube 6, and the auxiliary tube 7 can be achieved, significantly improving the flexibility and accuracy of the separation process.

[0151] Please see Figure 2 In some embodiments, a retaining bracket 8 is also included, which is disposed above the rotating plate 2 for engaging the hose 3. The retaining bracket 8 has an engagement structure inside that matches the outer diameter of the hose 3, and is preferably made of a self-lubricating material such as polytetrafluoroethylene or silicone to reduce rotational friction. The central through hole of the retaining bracket 8 is coaxial with the through hole of the rotating plate 2 to ensure the dynamic balance of the hose 3 during high-speed rotation.

[0152] In some embodiments, the tube body 4 is configured as a test tube and also includes a cover plate that covers the end of the tube body 4. The hose 3 is airtightly connected to the cover plate, and the inlet pipe 5 and outlet pipe 6 are airtightly connected to the tube body 4. The cover plate can be a rubber stopper or a plastic cover plate to ensure the formation of a sealed fluid passage.

[0153] In some embodiments, the rotating plate 2 is configured as a curved plate or a polygonal plate, such as a disk, a sector plate, or a rectangular plate. The drive unit 1 can be configured as a bidirectional servo motor to meet different testing requirements.

[0154] Furthermore, the following specific application examples are provided to facilitate understanding of the above technical solutions:

[0155] Example 1: Intermittent Cell Concentration

[0156] like Figure 1As shown, liquid containing cells is continuously pumped to the bottom of tube 4 through a feed pump and feed pipe 5 (feed pipe 5) in a flexible tube (i.e., hose 3). A drive motor (i.e., drive unit 1) drives a rotating rod (i.e., rotating plate 2) to rotate at high speed. The flexible tube (i.e., hose 3) passing through a hole (i.e., first through hole 21) on the rotating rod (i.e., rotating plate 2) drives tube 4 to rotate synchronously, achieving centrifugation. Under centrifugal force, the cells gradually settle to the bottom of tube 4, while the liquid at the top of the tube remains at the top. The liquid at the top of the tube is continuously discharged to a waste liquid collection device through discharge pipe 6 (i.e., discharge pipe 6) in the flexible tube (i.e., hose 3). When the cells in tube 4 reach a predetermined concentration factor, feeding, discharging, and centrifugation are stopped. Then, by reversing the operation of the feed pump or introducing washing solution from feed pipe 5 (i.e., feed pipe 5), the concentrated cells are discharged from the bottom of tube 4.

[0157] Example 2: Continuous Cell Concentration

[0158] like Figure 6 As shown, unlike Embodiment 1, the bottom of the tube 4 is provided with a bottom outlet (i.e., auxiliary tube 7). By precisely controlling the feed rate of the feed pump and the discharge rates of the top discharge pipe 6 (i.e., discharge pipe 6) and the bottom outlet (i.e., auxiliary tube 7), continuous feeding of liquid containing cells, continuous discharge of liquid at the top of the tube, and continuous collection of concentrated cells can be achieved. For example, the discharge rate of the bottom outlet (i.e., auxiliary tube 7) can be controlled to be much smaller than the feed rate, thereby achieving gradual concentration and continuous output of cells.

[0159] The specific method steps of the above embodiments are as follows:

[0160] (1). Feeding: The liquid containing cells is continuously transported to the bottom of the tube body 4 through the feed pipe 5 of the flexible tube (i.e., the flexible tube 3).

[0161] (2) Centrifugation: The drive mechanism (i.e., drive unit 1) drives the tube body 4 connected to the flexible tube (i.e., flexible hose 3) to rotate, generating a centrifugal force field. The drive mechanism (i.e., drive unit 1) is driven by a motor to rotate the rotating plate 2 (i.e., rotating plate 2). One end of the flexible wire (i.e., flexible hose 3) is fixed to the upper or lower end of the centrifugal shaft (i.e., fixed frame 8), and then passes through the hole (i.e., first through hole 21) on the rotating rod or disc (i.e., rotating plate 2) driven by the motor, with the tube body 4 at the end. When the rod or disc (i.e., rotating plate 2) rotates, it drives the flexible wire (i.e., flexible hose 3) and the tube body 4 to rotate, achieving the purpose of centrifugation. During the rotation, the flexible wire (i.e., flexible hose 3) automatically resets or maintains a certain twisted state through its own anti-torsion force. The flexible wire (i.e., flexible hose 3) has a pipe inside and the tube body 4 to realize the entry and exit of liquid. The hardness of the flexible wire (i.e., flexible hose 3) is maintained so that the degree of twist during rotation does not affect the liquid flow in the internal pipe, realizing continuous feeding and discharging. The flexible tube (i.e., hose 3) has five feed tubes (i.e., feed pipes 5) extending to the bottom of the tube body 4, and six discharge tubes (i.e., discharge pipes 6) located at the top of the tube body 4. During centrifugation, the centrifugal force is greater at the far end (bottom) of the tube body 4 from the center of rotation, where cells are located; the centrifugal force is smaller at the near end (top) of the tube body 4 from the center of rotation, mainly consisting of liquid and some low-density cell fragments, which is the discharge port. Cell concentration is achieved through continuous feeding and discharging. After reaching a certain concentration factor, feeding, discharging, and centrifugation are stopped, and the concentrated cells are then discharged through the feed port. The rotating flexible tube automatically resets or maintains a certain torsional state through its own anti-torsion force, ensuring the unobstructed flow of the internal channels. Bearings can be installed on the flexible tube (hose 3) to reduce friction with the rotating rod or disc holes.

[0162] (3). Concentration: Under the action of centrifugal force, the cells settle to the far end (bottom) of tube 4, forming a concentrated cell precipitate, while the upper liquid and cell debris with lower density are located at the near end (top) of tube 4.

[0163] (4). Discharge:

[0164] Top discharge (Example 1): The liquid and some impurities located at the top of the pipe body 4 are continuously discharged through the discharge pipe 6 (i.e. discharge pipe 6) of the flexible pipe (i.e. hose 3).

[0165] Bottom intermittent discharge (Example 2): When the cells in the tube 4 reach the predetermined concentration factor, feeding, discharging and centrifugation are stopped, and the concentrated cells are discharged through the feed pipe 5 (i.e., feed pipe 5) or the bottom discharge port (i.e., auxiliary pipe 7).

[0166] Bottom continuous discharge (Example 2): Concentrated cells are continuously collected through an independent bottom discharge port (i.e., auxiliary pipe 7). By precisely controlling the top discharge rate and the bottom discharge rate, continuous feeding, continuous top discharge, and continuous bottom concentrated cell discharge are achieved.

[0167] The specific structure of the above embodiment is as follows:

[0168] A continuous feeding centrifugal cell concentration device based on flexible tube drive, comprising:

[0169] Tube 4: Used to hold the liquid containing cells to be separated.

[0170] The flexible tube (i.e., hose 3) has at least two independent internal pipes: one is the feed pipe 5, whose inlet end is connected to the feed pump and whose outlet end extends to the bottom of the tube body 4; the other is the discharge pipe 6, whose inlet end is located at the top of the tube body 4 and whose outlet end is connected to the waste liquid collection device. In Embodiment 1, the flexible tube may consist only of the feed pipe 5 and the top discharge pipe 6.

[0171] The drive mechanism (i.e., drive unit 1) includes a motor and a rotating component (such as a rotating rod or disc, i.e., rotating plate 2). The rotating component (i.e., rotating plate 2) has a hole (i.e., a first through hole 21), through which a flexible tube (i.e., a flexible hose 3) passes. One end of the flexible tube is fixed to the upper or lower end of the centrifugal shaft. When the motor drives the rotating component to rotate, the flexible tube drives the tube body 4 to rotate synchronously, achieving centrifugation. To reduce friction, a bearing can be installed at the contact point between the flexible tube and the hole in the rotating component.

[0172] Feed pump: Used to pump liquid containing cells into the tube body 4 at a certain flow rate.

[0173] Discharge control mechanism (optional): In embodiment two, it is used to precisely control the flow rate of top discharge and bottom discharge.

[0174] Bottom outlet (optional): Located at the bottom of tube 4, for intermittent or continuous collection of concentrated cells.

[0175] The flexible tubing needs to possess a certain degree of flexibility to bend during rotation, while also having sufficient resistance to torsion to ensure the unobstructed flow of the five internal inlet pipes and six outlet pipes. The flexible tubing can be made of biocompatible materials such as medical-grade silicone or polyurethane. The diameter and wall thickness of the internal channels can be designed according to specific application requirements.

[0176] The rotating rod or disc needs to have sufficient strength and balance to ensure stability during high-speed rotation. The size of the bore should match the outer diameter of the flexible tube, and bearings can be installed to reduce friction and wear.

[0177] The above embodiments have the following beneficial effects:

[0178] Simple structure and low cost: The flexible tube drives the tube body 4 to rotate, replacing the traditional complex transmission mechanism and reducing equipment costs.

[0179] Easy to operate and maintain: The continuous feeding and discharging design simplifies the operation process and reduces manual intervention. The replacement and maintenance of the flexible tube are also relatively simple.

[0180] Continuous concentration is possible: Through continuous feeding and discharging, especially with the bottom discharge port, continuous concentration and collection of cells can be achieved, improving processing efficiency.

[0181] Minimal cell damage: The actuation method of flexible tubes is relatively gentle, which can reduce shear force on cells and lower the risk of cell damage.

[0182] High controllability: By adjusting the feed rate and discharge rate, the cell concentration factor and processing speed can be flexibly controlled.

[0183] In the above technical solution, the cell concentration device includes a drive unit, a horizontally positioned rotating plate, a flexible tube passing through the rotating plate, a tube body connected to the flexible tube, and a conveying assembly consisting of an inlet pipe, an outlet pipe, an inlet valve, and an outlet valve. The control unit coordinates the rotation speed of the drive unit with the operating modes of the inlet and outlet valves to achieve continuous centrifugal concentration of the liquid containing cells. During rotation, the flexible tube maintains unobstructed internal flow channels due to its own anti-torsion properties. The tube body tends to be horizontal as the rotating plate rotates, forming a stable centrifugal field. The conveying assembly achieves continuous separation and recovery of cell precipitates through multi-mode flow rate regulation. This technical solution simplifies the device structure and reduces manufacturing costs through the combination of the flexible tube's anti-torsion properties and the horizontal tube body. The differential speed control strategy, where the inlet flow rate of the inlet valve is greater than the outlet flow rate of the outlet valve, combined with intermittent buffer flushing and a stepped discharge mode, achieves continuous processing while protecting cells sensitive to shear forces. The flexible tube's structural design allows it to autonomously maintain unobstructed flow channels during rotation, solving the common problems of pipe entanglement and blockage in traditional continuous flow centrifuges. The control unit's real-time monitoring of the centrifugal sediment thickness and adaptive flow rate adjustment of the feed and discharge valves significantly improve cell concentration efficiency and avoid the risk of contamination caused by manual intervention.

[0184] Finally, it should be noted that although the above embodiments have been described in the text and drawings of this application, this should not limit the scope of patent protection of this application. Any technical solutions that are based on the essential concept of this application and utilize the content described in the text and drawings of this application, resulting in equivalent structural or procedural substitutions or modifications, as well as the direct or indirect application of the technical solutions of the above embodiments to other related technical fields, are all included within the scope of patent protection of this application.

Claims

1. A method for cell concentration, characterized in that, This invention relates to a cell concentration device, which includes a tube and a delivery assembly. The tube is disposed at the downward-extending end of a flexible tube and is airtightly connected to the end of the flexible tube. The tube is used to hold the liquid containing cells to be concentrated. The delivery assembly includes an inlet pipe and an outlet pipe, both of which are disposed within the flexible tube. One end of the inlet pipe protrudes into the tube, and one end of the outlet pipe protrudes into the tube. The method includes: The drive hose rotates to produce anti-torsion deformation and drive the tube body that can hold liquid to rotate. During the rotation, the hose maintains the unobstructed flow channel through its own anti-torsion force. Activate the first pumping mode: The feed pipe continuously delivers cell-containing liquid to the bottom of the tube at a first preset flow rate; Simultaneously, the first pumping mode is activated: the discharge pipe discharges the liquid located at the top of the pipe at the second preset flow rate, forming a continuous centrifugal concentration process; When the amount of cell sediment accumulated at the bottom of the tube reaches the preset condition, switch to the second pumping mode; At the same time, adjust the discharge pipe to the second pumping mode to discharge the liquid located at the top of the pipe in a preset incremental flow rate mode.

2. The cell concentration method according to claim 1, characterized in that, The method includes: Setting a first speed threshold and driving the rotating plate to rotate, the hose generates anti-torsion deformation and drives the tube body to rotate, including: The control unit controls the drive unit to increase the rotation speed of the rotating plate to the first speed threshold at a preset acceleration rate; During acceleration, the hose torsion state is monitored in real time and the drive torque of the drive unit is dynamically adjusted to keep the hose within the allowable torsion range so that the hose body tends to rotate horizontally. Once the rotational speed stabilizes, the control unit activates the feed valve to inject balancing fluid into the tube at a low speed. Simultaneously, it monitors the hose deformation parameters and the tube's spatial posture to determine the horizontal state. The conditions for determining the horizontal state include the hose torsion fluctuation value being less than the preset torsion threshold, the angle between the tube axis and the horizontal plane being less than the preset angle, and the pressure fluctuation in the feed pipeline being stable within the preset allowable range.

3. The cell concentration method according to claim 2, characterized in that, The first pumping mode is configured as either continuous pumping or intermittent pumping; The first pumping mode is configured as either continuous pumping or intermittent pumping. The control unit synchronously activates the first pumping mode of the feed valve, controlling the feed valve to continuously deliver cell-containing liquid to the bottom of the tube through the feed pipe at a first preset flow rate, including: The control unit dynamically adjusts the first preset flow rate according to the real-time rotation speed of the rotating plate, so that the feed flow rate and centrifugal force maintain a preset proportional relationship. During the conveying process, the pressure change in the feed pipe is continuously monitored. When the pressure fluctuation exceeds the allowable range, the control unit automatically adjusts the opening of the feed valve to maintain stable conveying. In addition, the feed flow rate is adjusted according to the change in liquid level in the tube, based on a preset algorithm, to ensure that the liquid containing cells forms a stable feed diffusion layer at the bottom of the tube. The first pumping mode of the discharge valve is activated, and the liquid located at the top of the pipe is discharged through the discharge pipe at a second preset flow rate, forming a continuous centrifugal concentration process. The first preset flow rate is greater than the second preset flow rate, including: The control unit dynamically adjusts the second preset flow rate according to the real-time liquid level in the tube, so that the liquid discharge rate at the top of the tube and the liquid feeding rate containing cells are kept in dynamic balance. During the pumping process, the pressure change in the discharge pipe is continuously monitored. When abnormal pressure fluctuations are detected, the control unit automatically adjusts the opening of the discharge valve to maintain stable discharge. Simultaneously, based on the feedback of the solid-liquid interface position within the tube, the second preset flow rate is corrected in real time to ensure that the liquid containing cells is maintained within the preset fluctuation range and is not carried out.

4. The cell concentration method according to claim 1, characterized in that, The second pumping mode is configured as either continuous pumping or intermittent pumping; The second pumping mode is configured as either continuous pumping or intermittent pumping; When the control unit detects that the accumulation of cell sediment at the bottom of the tube has reached a preset condition, it switches the feed valve to the second pumping mode, including: The control unit automatically adjusts the pulse frequency and single injection volume of the buffer solution based on the amount of cell sediment accumulation, so that the flushing effect is evenly distributed in the cell sediment. After each pulse injection, a preset time is allowed to allow the buffer solution to fully infiltrate, while the structural changes of the cell sediment are monitored, and the parameters of subsequent pulses are dynamically adjusted. And, simultaneously adjusting the second pumping mode of the discharge valve to discharge the liquid located at the top of the pipe at an increasing flow rate, including: The control unit sets the initial flow rate based on the rate of change of cell sediment accumulation, and automatically increases the discharge flow rate each time a threshold for decreasing accumulation is reached. After the discharge flow rate jumps, it maintains a stable discharge until the concentration of liquid containing cells in the tube drops to a preset critical value, and then enters the next flow rate adjustment cycle to ensure that the liquid at the top of the tube maintains a constant target concentration during continuous discharge.

5. The cell concentration method according to claim 1, characterized in that, The method further includes: During cell concentration, the control unit injects an auxiliary medium into a specific area within the tube via an auxiliary tube, including: When an abnormal accumulation of cell sediment is detected, the auxiliary valve is controlled to inject density-adjusting fluid in a pulse manner to improve the uniformity of cell sediment. Based on real-time monitoring of the solid-liquid interface position, a dynamic isolation layer is formed by injecting buffer solution through an auxiliary tube to prevent cell resuspension. After concentration is complete, the auxiliary valve is fully opened, and the cleaning solution is injected back into the tube body through the auxiliary tube to achieve efficient recovery of cell sediment.

6. The cell concentration method according to claim 1, characterized in that, The method further includes: The auxiliary tube extends to the bottom of the tube body, and the port of the auxiliary tube inside the tube body is higher than the port of the feed tube inside the tube body. When the control unit detects that the accumulation of cell sediment at the bottom of the tube has reached a preset condition: Adjust the feed valve to the second pumping mode to intermittently inject buffer solution to flush out cell sediment; adjust the auxiliary valve to the third pumping mode to gradually increase the flow rate to discharge cell sediment; the third pumping mode is configured to be continuous or intermittent pumping. Alternatively, the feed valve can be adjusted to the third pumping mode to continuously inject the liquid containing cells to be concentrated. The third pumping mode is configured as continuous or intermittent pumping. The auxiliary valve can be adjusted to the fourth pumping mode to discharge the cell sediment in a step-by-step increasing flow rate mode. The fourth pumping mode is configured as continuous or intermittent pumping. In addition, adjust the discharge valve to the second pumping mode to discharge the liquid located at the top of the pipe; Keep the drive unit rotating at a constant speed until the liquid at the top of the tube is completely discharged. During the rotation, the hose maintains the smooth flow of the internal channel through its own anti-torsion force.

7. A cell concentration device, characterized in that, The apparatus is applicable to the method according to any one of claims 1 to 6, wherein the apparatus comprises: Drive unit; A rotating plate is disposed at the output end of the driving unit. The rotating plate is arranged horizontally. The driving unit is used to drive the rotating plate to rotate. The rotating plate is provided with at least one first through hole. A flexible tube passes through the rotating plate from top to bottom through the first through hole, and the number of the flexible tubes corresponds to the number of the first through holes. A tube body is disposed at one of the downwardly extending ends of the flexible tube, and the tube body is airtightly connected to the end of the flexible tube. The tube body is used to hold the liquid containing cells to be concentrated. The conveying assembly includes an inlet pipe, an outlet pipe, an inlet valve, and an outlet valve. The inlet pipe and the outlet pipe are both disposed inside the flexible hose. One end of the inlet pipe protrudes into the hose body, and one end of the outlet pipe protrudes into the hose body. The inlet pipe is provided with an inlet valve, and the outlet pipe is provided with an outlet valve. The control unit is electrically connected to the feed valve, the discharge valve, and the drive unit. The control unit is used to control the rotation speed of the drive unit and to control the pumping mode of the feed valve and the pumping mode of the discharge valve during the rotation of the rotating plate.

8. The cell concentration apparatus according to claim 7, characterized in that, The length of the feed pipe extending into the tube body is different from the length of the discharge pipe extending into the tube body.

9. The cell concentration apparatus according to claim 7, characterized in that, The conveying assembly also includes: An auxiliary tube is disposed inside the flexible tube, with one end of the auxiliary tube protruding into the tube body; An auxiliary valve is disposed on the auxiliary pipe and is electrically connected to the control unit.

10. The cell concentration apparatus according to claim 7, characterized in that, The length of the auxiliary pipe protruding into the pipe body is different from the length of the discharge pipe protruding into the pipe body; Alternatively, the length of the auxiliary tube protruding into the tube body is different from the length of the feed tube protruding into the tube body.

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