Cell concentration device and method for controlling cell concentration

Abstract

The invention provides a cell concentration device and a cell concentration control method, and belongs to the technical field of cell concentration. The cell concentration device comprises a body, at least two transducers, a container moving assembly and a control module, a containing groove is formed in the body and used for containing a cell bearing container, and a to-be-concentrated sample is stored in the cell bearing container; the two transducers are arranged on the two side faces of the containing groove respectively, the transducers are attached to the cell bearing container, and the transducers are used for converting electric signals into mechanical vibration to generate sound waves; the container moving assembly is arranged on the body and is used for lifting or lowering the cell bearing container; wherein the control module controls the two transducers to generate sound waves; meanwhile, the container moving assembly is controlled to lift the cell bearing container, so that cells in the sample are concentrated at the bottom of the cell bearing container under the action of the sound waves. The invention aims to solve the problems that the safety and integrity of concentrated cells are relatively low, the cell concentration time is long, and the cells are easy to damage.

Description

Technical Field

[0001] The present invention belongs to the technical field of cell concentration, and in particular relates to a cell concentration device and a cell concentration control method. Background Art

[0002] Cell concentration is an essential operation in various biological and biomedical research and production processes, including cell culture, cell analysis, and diagnostic assays. Existing methods typically use centrifugation to concentrate cells. This involves spinning the sample at high speed in a centrifuge to separate the cells from the surrounding medium based on their density and size. However, this method can cause cell damage and is not suitable for fragile or sensitive cells.

[0003] Existing methods can also separate cells from liquid culture media through filtration using porous membranes or filters. Although this method is suitable for fragile cells, there is the problem of filter clogging, and the concentration process usually takes a long time.

[0004] Therefore, existing cell concentration methods have problems such as low safety and integrity of concentrated cells, long cell concentration time, high cell concentration cost, and easy cell damage. Summary of the Invention

[0005] The present invention proposes a cell concentration device and a cell concentration control method, aiming to solve the problems of low safety and integrity of concentrated cells, long cell concentration time, high cell concentration cost, and easy cell damage.

[0006] In a first aspect, the present application provides a cell concentration device comprising a body, at least two transducers, a container movement assembly, and a control module;

[0007] The body is formed with a receiving groove, the receiving groove is used to place a cell-carrying container, and the cell-carrying container stores a sample to be concentrated;

[0008] The two transducers are respectively arranged on two sides of the containing tank, the transducers are attached to the cell-carrying container, and the transducers are used to convert electrical signals into mechanical vibrations to generate sound waves;

[0009] The container moving assembly is disposed on the body and is used to lift or lower the cell-carrying container;

[0010] The control module is arranged on the body and connected to the transducer and the container moving assembly;

[0011] Among them, the control module controls the two transducers to generate sound waves so that the two transducers simultaneously transmit the sound waves to the cell-carrying container; and at the same time controls the container moving component to lift the cell-carrying container so that the cells in the sample are concentrated at the bottom of the cell-carrying container due to the action of the sound waves.

[0012] Optionally, the container moving assembly is also connected to the cell-carrying container; wherein the control module is used to control the container moving assembly to rotate and rise, so as to drive the cell-carrying container to rotate and rise, so that the cells in the sample are concentrated at the bottom of the cell-carrying container due to the action of the sound waves.

[0013] Optionally, a coupling agent is applied to the surface of the transducer that is in contact with the cell-carrying container.

[0014] Optionally, the two transducers are symmetrically arranged on two side surfaces of the accommodating groove, and the working parameters of the two transducers are the same.

[0015] Optionally, the operating parameters include at least frequency and excitation voltage, the frequency of the transducer is determined according to the node position of the sound wave and the sound wave radiation intensity, and the excitation voltage is determined according to the particle size of the particles in the sample during concentration.

[0016] Optionally, the frequency range of the transducer is 1 MHz-5 MHz; the excitation voltage range of the transducer is 30-120 V.

[0017] Optionally, the sample liquid surface of the cell-holding container is at least flush with the upper end of the transducer.

[0018] Optionally, the cell-carrying container comprises a centrifuge tube.

[0019] Optionally, when the bottom of the centrifuge tube rises to a position flush with the middle of the transducer, the control module controls the container moving assembly to gradually reduce the rising speed of the cell-carrying container until the centrifuge tube stops rising.

[0020] Optionally, the rotation speed and the rising speed of the cell holding container are determined according to the size of the cell holding container.

[0021] Optionally, the transducer is a piezoelectric lead zirconate titanate transducer.

[0022] In a second aspect, the present application further provides a method for controlling cell concentration, which is applied to the cell concentration device as described above; the method comprises:

[0023] placing a cell-carrying container containing a sample to be concentrated in a receiving tank of the cell concentrator;

[0024] controlling the two transducers to simultaneously propagate sound waves toward the cell-carrying container;

[0025] The container moving assembly is controlled to lift the cell holding container, so that the cells in the sample are concentrated at the bottom of the cell holding container due to the action of the sound waves.

[0026] Optionally, the method further includes:

[0027] determining the frequency of the transducer according to the node positions and the radiation of the acoustic wave, and / or determining the excitation voltage of the transducer according to the particle size of the particles in the sample during concentration, and / or determining the rotation speed and the rising speed of the cell holding container according to the size of the cell holding container;

[0028] controlling the transducer to convert the electrical signal into mechanical vibration according to the frequency and the excitation voltage to generate sound waves;

[0029] The container moving assembly is controlled to lift the cell holding container at the ascending speed, and the container moving assembly is simultaneously controlled to rotate the cell holding container at the rotating speed, so that the cells in the sample are enriched at the bottom of the cell holding container due to the action of the sound waves.

[0030] The present application provides a cell concentration device and a control method for cell concentration, which includes a body, at least two transducers, a container moving assembly and a control module. The body is formed with a receiving groove, the receiving groove is used to place a cell carrying container, and the cell carrying container stores a sample to be concentrated; two transducers are respectively arranged on both sides of the receiving groove, the transducers are fitted with the cell carrying container, and the transducers are used to convert electrical signals into mechanical vibrations to generate sound waves; the container moving assembly is arranged on the body, for lifting or lowering the cell carrying container; the control module is arranged on the body and connected to the transducer and the container moving assembly; wherein the control module controls the two transducers to generate sound waves so that the two transducers simultaneously transmit sound waves to the cell carrying container; at the same time, the container moving assembly is controlled to lift the cell carrying container so that the cells in the sample are concentrated at the bottom of the cell carrying container due to the action of the sound waves. In this way, damage to the cells in the sample caused by large centrifugal force and high centrifugal speed can be avoided, cell concentration can be achieved without centrifugal force, it can adapt to most scenarios, improve the safety and integrity of the concentrated cells, while reducing the time and cost of cell concentration, and can maintain higher cell activity. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the following is a brief introduction to the drawings required for use in the description of the embodiments. Obviously, the drawings described below are some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without any creative work.

[0032] Figure 1 A schematic structural diagram of a cell concentration device provided in an embodiment of the present application;

[0033] Figure 2 A schematic structural diagram of another cell concentration device provided in an embodiment of the present application;

[0034] Figure 3 A schematic diagram of the working principle of a cell concentration device provided in an embodiment of the present application;

[0035] Figure 4 A schematic diagram of the sound pressure distribution in a cell-carrying container in an initial state provided in an embodiment of the present application;

[0036] Figure 5 A schematic diagram of the sound pressure distribution in a cell-carrying container when the cell-carrying container is taken out according to an embodiment of the present application;

[0037] Figure 6 A schematic flow chart of the steps of a cell concentration control method provided in an embodiment of the present application;

[0038] Figure 7 A schematic flow chart of another method for controlling cell concentration provided in an embodiment of the present application;

[0039] Figure 8 A schematic diagram of the concentration changes of three types of polystyrene microspheres before and after concentration using a cell concentration device provided in an embodiment of the present application;

[0040] Figure 9 A schematic diagram of the concentration changes of three types of cells before and after concentration using a cell concentration device provided in an embodiment of the present application;

[0041] Figure 10 This is a schematic diagram of the cell viability results before and after concentration of a cell concentration device provided in an embodiment of the present application. DETAILED DESCRIPTION

[0042] The following will be combined with the drawings in the embodiments of this application to clearly and completely describe the technical solutions in the embodiments of this application. Obviously, the embodiments described are part of the embodiments of this application, not all of them. Based on the embodiments in this application, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of this application.

[0043] The flowcharts shown in the accompanying drawings are for illustrative purposes only and do not necessarily include all contents and operations / steps, nor must they be executed in the order described. For example, some operations / steps may be decomposed, combined, or partially merged, so the actual execution order may vary depending on the actual situation.

[0044] It should be understood that the terms used in this specification are only for the purpose of describing specific embodiments and are not intended to limit the present application. As used in this specification and the appended claims, the singular forms "a", "an", and "the" are intended to include the plural forms unless the context clearly indicates otherwise.

[0045] It will also be understood that the term "and / or" used in this specification and the appended claims refers to and includes any and all possible combinations of one or more of the associated listed items.

[0046] The following describes some embodiments of the present application in detail with reference to the accompanying drawings. In the absence of conflict, the following embodiments and features therein may be combined with each other.

[0047] Cell concentration is an indispensable operation in various biological and biomedical research and production processes, such as cell culture, cell analysis and diagnostic assays. Currently, multiple methods can be used to concentrate cells, each with its own advantages and limitations.

[0048] (1) Centrifugation is one of the most commonly used methods for cell concentration. The sample is spun at high speed in a centrifuge to separate cells from the surrounding medium based on their density and size. However, this common method may cause cell damage and is not suitable for fragile or sensitive cells.

[0049] (2) The filtration method is to separate cells from the liquid culture medium by using a porous membrane or filter. It is suitable for fragile cells, but there is a problem of filter clogging, and the concentration process usually takes longer.

[0050] (3) Microfluidics methods use microchannels integrated with fluid mechanics and / or acoustic vibrations to perform precise cell manipulation and concentration. However, the development and customization of microfluidics devices required to achieve the concentration of specific cells are not suitable for processing large sample volumes and are highly complex.

[0051] (4) Magnetic separation methods require the use of magnetic particles to label cells and use magnetic fields to concentrate and separate labeled cells. This method requires the use of magnetic particles, which may affect cell behavior or downstream applications.

[0052] (5) Density gradient centrifugation methods can layer samples on density gradient media and centrifuge them, but the gradient needs to be carefully optimized and may not be suitable for all cell types.

[0053] (6) The ultrafiltration method is to push cells through a semipermeable membrane with a specific pore size at a certain pressure to achieve cell separation, but this method cannot effectively retain smaller cells.

[0054] The choice of the above cell concentration methods is determined by factors such as cell type, required purity, sample amount, and downstream application. Researchers and clinicians select the most appropriate method based on their specific needs and available resources. However, the development of rapid and safe cell concentration methods remains an ongoing need in the biomedical field.

[0055] Among the related technologies, ultrasonic technology based on piezoelectric lead zirconate titanate (PZT) transducers has been used in clinical applications and basic research closely related to biomedicine. The standing waves generated by PZT transducers can stably manipulate cells and are used in tissue engineering, cell sorting, and organoids. However, existing PZT transducer sorting and cell concentration methods need to be combined with microfluidic technology, which can only achieve the concentration of cells in trace samples. It also requires the design of specially structured microfluidic devices and pressure pumps to promote liquid flow, and the system is highly complex. However, there is a lack of direct and rapid cell concentration methods for macroscopic large-scale containers such as centrifuge tubes commonly used in biotechnology.

[0056] To address the shortcomings of the above-mentioned prior art, the present application proposes a cell concentrator and a cell concentration control method. This cell concentrator can avoid damage to cells within a sample caused by high centrifugal forces and high centrifugal speeds, achieve cell concentration without centrifugal force, adapt to most scenarios, improve the safety and integrity of concentrated cells, reduce the time and cost of cell concentration, and maintain higher cell activity.

[0057] See also Figure 1 , Figure 1 This is a schematic structural diagram of a cell concentration device provided in an embodiment of the present application. Figure 2 This is a schematic structural diagram of another cell concentration device provided in an embodiment of the present application.

[0058] like Figure 1 and Figure 2As shown, the cell concentration device 100 includes a body 10, at least two transducers 20, a container moving assembly 30, and a control module. The body 10 is formed with a receiving tank 11, which is used to place a cell-carrying container 12. The cell-carrying container 12 stores the sample to be concentrated. The width of the receiving tank 11 can be determined according to the size of the cell-carrying container 12. The shape of the cell-carrying container 12 can be various shapes, which can be determined according to actual conditions. The sample to be concentrated can be a cell suspension to be concentrated, etc. Two transducers 20 are respectively arranged on the two sides of the receiving tank 11. The transducers 20 are in contact with the cell-carrying container 12. The transducers 20 are used to convert electrical signals into mechanical vibrations to generate sound waves. The transducers 20 are in contact with the cross-section of the cell-carrying container 12, so that the cell-carrying container 12 can rise while being as close to the transducer 20 as possible. The container moving assembly 30 is disposed on the body 10 and is used to raise or lower the cell-carrying container 12. The container moving assembly 30 is connected to the cell-carrying container 12 and can move the cell-carrying container 12 upward or downward. A control module is disposed on the body 10 and is connected to the transducer 20 and the container moving assembly 30. The control module can be disposed inside or outside the body 10. The control module is used to control the transducer 20 to convert electrical signals into mechanical vibrations to generate sound waves, and is also used to control the container moving assembly 30 to raise or lower the cell-carrying container 12.

[0059] It should be noted that the cell concentrating device 100 may include at least two transducers 20, which are respectively arranged on the two side surfaces of the receiving tank 11. In order to improve the intensity and efficiency of the action, two transducers 20 may also be respectively arranged on the two side surfaces of the receiving tank 11. No specific limitation is made here.

[0060] Specifically, the control module can be used to control the two transducers 20 to generate sound waves simultaneously, so that the two transducers 20 can simultaneously transmit sound waves to the cell-carrying container 12; at the same time, the container moving component 30 can be controlled to lift the cell-carrying container 12, so that the cells in the sample are enriched at the bottom of the cell-carrying container 12 due to the action of the sound waves. The present application realizes cell concentration through the principle of sound wave propagation, and can achieve lossless enrichment of cells without the need for centrifugal force.

[0061] For example, the control module can be used to control the container moving assembly 30 to lower, thereby driving the cell holding container 12 to descend to the corresponding acoustic wave action position (ie, Figure 1 Initial position shown). Figure 3 and Figure 4As shown, the control module then controls the two transducers 20 to generate sound waves simultaneously, so that the two transducers 20 simultaneously propagate sound waves toward the cell-carrying container 12. At this time, the sound waves generated by the two transducers 20 propagate in opposite directions. The two sound waves form antinodes at the points where the voltages are added, and nodes at the points where the voltages are subtracted. At the nodes, due to the subtraction of the signals of the two sound waves, the particle motion here is relatively stationary. Therefore, when cells are placed in the cell-carrying container 12, the cells can gather at the nodes and form a linear arrangement at the nodes. Figure 5 As shown, the container moving assembly 30 is controlled to slowly rise, thereby driving the cell holding container 12 to rise, so that the cells in the sample are slowly enriched at the bottom of the cell holding container 12 due to the action of the sound waves. The present application realizes cell concentration through the principle of sound wave propagation, and cell concentration can be achieved without centrifugal force.

[0062] The present application provides a cell concentrator 100, which includes a body 10, at least two transducers 20, a container moving assembly 30, and a control module. The body 10 is formed with a receiving tank 11, which is used to place a cell-carrying container 12, which stores a sample to be concentrated; two transducers 20 are respectively arranged on both sides of the receiving tank 11, and the transducers 20 are attached to the cell-carrying container 12. The transducers 20 are used to convert electrical signals into mechanical vibrations to generate sound waves; the container moving assembly 30 is arranged on the body 10 and is used to lift or lower the cell-carrying container 12; the control module is arranged on the body 10 and is connected to the transducers 20 and the container moving assembly 30; wherein the control module controls the two transducers 20 to generate sound waves so that the two transducers 20 simultaneously transmit sound waves to the cell-carrying container 12; and at the same time controls the container moving assembly 30 to lift the cell-carrying container 12 so that the cells in the sample are concentrated at the bottom of the cell-carrying container 12 due to the action of the sound waves. This can avoid damage to cells in the sample caused by large centrifugal force and high centrifugal speed, and achieve cell concentration without centrifugal force. It can adapt to most scenarios, improve the safety and integrity of the concentrated cells, and reduce the time and cost of cell concentration, while maintaining higher cell activity.

[0063] In some embodiments, the container moving assembly 30 is further connected to the cell holding container 12; the control module is configured to control the container moving assembly 30 to rotate and ascend, thereby driving the cell holding container 12 to rotate and ascend, causing the cells in the sample to concentrate at the bottom of the cell holding container 12 due to the action of the sound waves. This allows the cell holding container 12 to rotate and ascend, allowing the sound waves to fully react with the sample in the cell holding container 12, so that the majority of the cells in the sample are concentrated at the bottom of the cell holding container 12 due to the action of the sound waves.

[0064] If the control module is only used to control the upward movement of the container moving assembly 30 to drive the cell holding container 12 upward, the sound waves generated by the transducer 20 can only act on the side of the cell holding container 12 that is in contact with the transducer 20. The sound waves on the side of the cell holding container 12 that is not in contact with the transducer 20 (the side perpendicular to the transducer 20) are less effective. As a result, the cells in the sample may not be completely concentrated at the bottom of the cell holding container 12, resulting in a poor cell concentration effect.

[0065] Specifically, the container moving assembly 30 can be controlled by the control module to rotate and rise. Since the container moving assembly 30 is connected to the cell holding container 12, when the container moving assembly 30 rotates and rises, the cell holding container 12 will follow the container moving assembly 30 and rotate and rise synchronously at the same rate, so that the sound waves can act on all surfaces of the cell holding container 12, thereby causing most of the cells in the sample to be concentrated at the bottom of the cell holding container 12 due to the action of the sound waves.

[0066] In some embodiments, a coupling agent is applied to the surface of the transducer 20 that contacts the cell holding container 12 . This can reduce energy loss during the propagation of sound waves, improve the utilization rate of sound waves, and allow sound waves to effectively enter the cell holding container 12 .

[0067] Among them, sound waves experience significant losses when propagating in non-continuous media. The characteristic of sound waves is that they lose the least energy in continuous media. If strong reflection occurs at the boundary of a medium with a particularly large difference in impedance (the product of sound velocity and density), energy will be greatly lost. Therefore, to reduce the influence of gas and non-continuous media between the ultrasonic transmission medium, the transducer 20 needs to be tightly fitted to the container wall of the cell-holding container 12, and a coupling agent needs to be applied to the surface of the transducer 20 that contacts the cell-holding container 12 to reduce energy loss during sound wave propagation and ensure that the sound wave effectively enters the cell-holding container 12.

[0068] For example, the coupling agent may include water, glycerin, mineral oil, silicone oil, and other media that can be used to propagate sound waves.

[0069] In some embodiments, two transducers 20 are symmetrically arranged on opposite sides of the receiving groove 11, and the operating parameters of the two transducers 20 are the same. Thus, the two transducers 20 can be configured with the same operating parameters, thereby emitting sound waves of the same frequency, thereby causing cells to aggregate at the nodes, where they are linearly arranged, thereby achieving the effect of cell aggregation.

[0070] Specifically, the two transducers 20 can be symmetrically arranged on the two sides of the accommodating groove 11 with respect to the center of the accommodating groove 11, so that the two transducers 20 are at the same distance from the center of the accommodating groove 11. At the same time, the two transducers 20 are set with the same working parameters, so that the two transducers 20 can emit sound waves of the same frequency, thereby enabling the cells to gather at the points of the wave nodes, and the cells are arranged linearly at the wave nodes, thereby achieving a centrifugal effect.

[0071] For example, the operating parameters of the transducer 20 may include parameters such as frequency and power. The two transducers 20 may be set to the same parameters such as frequency and power, so that the two transducers 20 can emit sound waves of the same frequency and operate in substantially the same manner. It should be noted that any operating parameters of the two transducers 20 need to be set to the same parameters.

[0072] In some embodiments, operating parameters include at least frequency and excitation voltage. The frequency of transducer 20 is determined based on the acoustic wave node locations and acoustic wave radiation intensity, while the excitation voltage is determined based on the particle size of the sample during concentration. Thus, the frequency of transducer 20 can be determined based on the acoustic wave node locations and acoustic wave radiation intensity, and the excitation voltage can be adjusted based on the particle size of the sample during concentration, thereby optimizing the cell concentration effect. This also enables the cell concentrator 100 to adjust operating parameters for particles, cells, and other substances with different diameters.

[0073] Specifically, the size of the particles separated by the centrifuge tube can be changed by changing the frequency of the transducer 20. The excitation voltage of the transducer 20 can also be adjusted according to the particle size of the particles in the sample during concentration to achieve the best cell concentration effect.

[0074] For example, if the cell-carrying container 12 is required to separate particles with larger diameters and volumes, such as particles with a diameter of 30 μm, the transducer 20 needs to be set to a smaller frequency, so that the node width of the wave node becomes larger, thereby enabling the wave node to gather larger particles, and finally allowing the cell-carrying container 12 to separate larger particles.

[0075] For example, if the cell-carrying container 12 is required to separate particles with smaller diameters and volumes, such as particles with a diameter of 5 μm, the transducer 20 needs to be set to a higher frequency so that the node width of the wave node becomes smaller, thereby enabling the wave node to gather smaller particles, and finally allowing the cell-carrying container 12 to separate smaller particles.

[0076] For example, if the cell-carrying container 12 is required to separate particles with larger diameters and volumes, such as particles with a diameter of 30 μm, since the movement speed of particles in the sample is faster when large particles are concentrated, a smaller excitation voltage of the transducer 20 can be set to achieve the best cell concentration effect.

[0077] For example, if the cell-carrying container 12 needs to be separated to obtain particles with smaller diameter and volume, such as particles with a diameter of 5 μm, since the movement speed of particles in the sample is slower when small particles are concentrated, a larger excitation voltage of the transducer 20 can be set to achieve the best cell concentration effect.

[0078] It should be noted that the excitation voltage is inversely proportional to the particle size during enrichment, but if the particle movement speed is too slow, the concentration efficiency will be low, and if the excitation voltage is too high, it will cause significant heat and cannot ensure biosafety. Therefore, the excitation voltage needs to be adjusted according to the actual situation.

[0079] In some embodiments, the frequency range of the transducer 20 is 1 MHz to 5 MHz, and the excitation voltage range of the transducer 20 is 30 to 120 V. Thus, by adjusting the frequency range and excitation voltage range of the transducer 20, the node width range of the acoustic wave generated by the transducer 20 and the movement speed of the particles in the sample can be limited.

[0080] For example, the frequency range of the transducer 20 may be determined according to the node position of the sound wave and the radiation intensity of the sound wave. For example, the frequency of the transducer 20 may be 1 MHz, 2.5 MHz, or 5 MHz.

[0081] For example, the excitation voltage range of the transducer 20 may be determined according to the movement speed of particles in the sample during concentration. For example, the excitation voltage of the transducer 20 may be 30V, 80V, or 120V.

[0082] In some embodiments, the sample liquid level in the cell holding container 12 is at least flush with the upper end of the transducer 20. This allows all cells in the sample in the cell holding container 12 to be concentrated under the acoustic waves of the transducer 20, thereby improving the cell concentration effect of the cell concentrator 100.

[0083] The acoustic wave propagation area of the transducer 20 is the area corresponding to the propagation path of the acoustic wave from the transducer 20 to the cell holding container 12. Generally, the two transducers 20 are symmetrically arranged on both sides of the receiving tank 11, so the acoustic wave propagation areas of the transducers 20 are also symmetrical.

[0084] Specifically, the control module can first control the container moving assembly 30 to rotate and lower, thereby driving the cell holding container 12 to rotate and descend to the corresponding acoustic wave action position, that is, the position where the sample liquid level in the cell holding container 12 is flush with the upper end of the transducer 20. The control module then controls the two transducers 20 to simultaneously generate acoustic waves, so that the two transducers 20 simultaneously transmit acoustic waves to the cell holding container 12. At this time, the acoustic waves generated by the two transducers 20 propagate in opposite directions, allowing cells to gather at the points of the wave nodes and form a linear arrangement at the wave nodes. The container moving assembly 30 is then controlled to slowly rotate and raise, thereby driving the cell holding container 12 to rotate and rise, so that the cells in the sample are gradually concentrated at the bottom of the cell holding container 12 due to the action of the acoustic waves.

[0085] In some embodiments, the cell-holding container 12 comprises a centrifuge tube.

[0086] The cell-carrying container 12 may be any container that can be used to carry a cell solution, and is not specifically limited herein. In actual use, other containers may be selected whose walls are in direct and continuous contact with the transducer 20 during the container rotation process.

[0087] In some embodiments, when the bottom of the centrifuge tube rises to a position flush with the middle of the transducer 20, the control module controls the container moving assembly 30 to gradually reduce the ascending speed of the cell-carrying container 12 until the centrifuge tube stops ascending. This prevents the container moving assembly 30 from stopping at a relatively high ascending speed, allowing the cells at the bottom to move to the middle of the centrifuge tube due to gravity.

[0088] Specifically, when the bottom of the centrifuge tube rises to a position flush with the middle of the transducer 20, the power can be shut down by stepping down the voltage. At this time, the control module will control the container moving assembly 30 to gradually reduce the rising speed and rotation speed of the cell-carrying container 12 until the centrifuge tube stops rising.

[0089] For example, when cell concentration is just beginning, the bottom of the centrifuge tube is generally located below the transducer 20. At this time, the control module can lift the container moving assembly 30 at a rising speed of 0.5 mm / s and rotate the container moving assembly 30 at a rotation speed of 0.6 revolutions / s, thereby driving the centrifuge tube to rotate and rise. When it is detected that the bottom of the centrifuge tube has risen to a position flush with the middle of the transducer 20, the control module can lift the container moving assembly 30 at a rising speed of 0.25 mm / s and rotate the container moving assembly 30 at a rotation speed of 0.3 revolutions / s. When it is detected that the bottom of the centrifuge tube is about to rise to a position flush with the upper end of the transducer 20, the control module can lift the container moving assembly 30 at a rising speed of 0.1 mm / s and rotate the container moving assembly 30 at a rotation speed of 0.1 revolutions / s until the bottom of the centrifuge tube rises to a position flush with the upper end of the transducer 20, at which time the control module controls the container moving assembly 30 to stop moving. In this way, the container moving assembly 30 gradually and slowly reduces the rising speed and the rotation speed, which can prevent the cells at the bottom from moving to the middle of the centrifuge tube due to the effect of gravity, and can achieve a better cell concentration effect.

[0090] For example, when cell concentration is just beginning, the bottom of the centrifuge tube is generally located below the transducer 20. At this time, the control module can raise the container moving assembly 30 at a rising speed of 0.5 mm / s and rotate the container moving assembly 30 at a rotation speed of 0.6 revolutions / s, thereby driving the centrifuge tube to rotate and rise. When it is detected that the bottom of the centrifuge tube has risen to a position flush with the middle of the transducer 20, the control module can raise the container moving assembly 30 at a rising speed of 0.25 mm / s and stop rotating the container moving assembly 30. When it is detected that the bottom of the centrifuge tube is about to rise to a position flush with the upper end of the transducer 20, the control module can raise the container moving assembly 30 at a rising speed of 0.1 mm / s until the bottom of the centrifuge tube rises to a position flush with the upper end of the transducer 20, at which point the control module controls the container moving assembly 30 to stop. In this way, the container moving assembly 30 gradually and slowly reduces its rising speed, which can prevent cells at the bottom from moving to the middle of the centrifuge tube due to gravity, thereby achieving a better cell concentration effect.

[0091] In some embodiments, the transducer 20 is a piezoelectric lead zirconate titanate transducer 20 .

[0092] The piezoelectric lead zirconate titanate transducer 20 is a piezoelectric ceramic material with excellent piezoelectric properties. The transducer 20 of this application utilizes the inverse piezoelectric effect, which causes the piezoelectric material to generate mechanical vibrations by applying an electrical signal. Lead zirconate titanate is a material used in piezoelectric transducers. It should be noted that any piezoelectric material can be used to manufacture the transducer 20 provided in this application.

[0093] Please refer to Figure 6 , Figure 6 A flow chart of a cell concentration control method provided in an embodiment of the present application is provided. This cell concentration control method can be applied to a cell concentrator 100, thereby avoiding damage to cells within a sample caused by large centrifugal forces and high centrifugal speeds. Cell concentration can be achieved without centrifugal force, adapting to most scenarios, improving the safety and integrity of concentrated cells, reducing the time and cost of cell concentration, and maintaining higher cell activity.

[0094] like Figure 6 As shown, the cell concentration control method may include S101 to S103.

[0095] S101 , placing a cell-carrying container containing a sample to be concentrated in a receiving tank of the cell concentrator.

[0096] S102: Control the two transducers to simultaneously propagate sound waves toward the cell-carrying container.

[0097] S103 , controlling the container moving assembly to lift the cell holding container, so that the cells in the sample are concentrated at the bottom of the cell holding container due to the action of the sound waves.

[0098] It should be noted that the specific method of converting electrical signals into mechanical vibrations to generate sound waves through a transducer can refer to the corresponding embodiments recorded in the specification of this application, and the specific method of lifting the cell-carrying container through the container moving component so that the cells in the sample are concentrated at the bottom of the cell-carrying container due to the action of the sound waves can refer to the corresponding embodiments recorded in the specification of this application, and this embodiment will not be repeated here.

[0099] like Figure 7 As shown, specifically, the cell concentration control method may further include S201 to S203.

[0100] S201: Determine the frequency of the transducer based on the node positions and acoustic wave radiation of the acoustic wave, and / or determine the excitation voltage of the transducer based on the particle size of particles in the sample during concentration, and / or determine the rotation speed and rising speed of the cell holding container based on the size of the cell holding container.

[0101] S202, controlling the transducer to convert the electrical signal into mechanical vibration according to the frequency and the excitation voltage to generate sound waves;

[0102] S203, controlling the container moving assembly to lift the cell holding container at the ascending speed, and simultaneously controlling the container moving assembly to rotate the cell holding container at the rotating speed, so that the cells in the sample are enriched at the bottom of the cell holding container due to the action of the sound waves.

[0103] Specifically, the frequency of the transducer can be determined based on the node locations and acoustic radiation of the acoustic wave. The excitation voltage of the transducer can also be determined based on the particle size of the sample during concentration. The rotational speed and rising speed of the cell holding container can also be determined based on the size of the cell holding container. It should be noted that the operating parameters of the transducer and the cell holding container can be determined based on actual conditions and are not specifically limited here.

[0104] Illustratively, after the cell concentration operation is performed by the cell concentration device provided by the present application, the concentrated cells are analyzed to obtain cell analysis results.

[0105] Among them, polystyrene microspheres of different particle sizes can be tested, as well as 293T, Hela, and HepG2 cells.

[0106] like Figure 8 As shown, the microsphere concentrations of 20 μm, 7 μm and 1 μm polystyrene microspheres were tested respectively. Figure 8 The bars from left to right in the figure represent the original microsphere concentration, the supernatant microsphere concentration, and the post-concentration microsphere concentration. After 40 seconds of treatment in the cell concentrator, the number of microspheres of varying sizes in the concentrated solution increased compared to the original solution microsphere concentration. The supernatant after cell concentration contained minimal particle / cell loss, essentially concentrating the sample. Therefore, it can be determined that the cells in the sample were largely concentrated at the bottom of the cell container due to the acoustic wave.

[0107] like Figure 9 As shown, the cell concentrations of 293T, Hela, and HepG2 cells were tested respectively. Figure 9 The bars from left to right represent the original cell concentration, supernatant cell concentration, and concentrated cell concentration, respectively. After 40 seconds of treatment in the cell concentrator, the number of concentrated microspheres of varying sizes increased compared to the original solution cell concentration. All three cell types were effectively concentrated, confirming that the cells in the sample were largely concentrated at the bottom of the cell container due to the acoustic wave.

[0108] like Figure 10 As shown, Figure 10 The results of cell activity after concentration show that there is no significant change in cell activity after concentration by the cell concentrator provided by the application, and the cell viability is higher than 95%.

[0109] The present application provides a cell concentration device and a control method for cell concentration, which includes a body, at least two transducers, a container moving assembly and a control module. The body is formed with a receiving groove, the receiving groove is used to place a cell carrying container, and the cell carrying container stores a sample to be concentrated; two transducers are respectively arranged on both sides of the receiving groove, the transducers are fitted with the cell carrying container, and the transducers are used to convert electrical signals into mechanical vibrations to generate sound waves; the container moving assembly is arranged on the body, for lifting or lowering the cell carrying container; the control module is arranged on the body and connected to the transducer and the container moving assembly; wherein the control module controls the two transducers to generate sound waves so that the two transducers simultaneously transmit sound waves to the cell carrying container; at the same time, the container moving assembly is controlled to lift the cell carrying container so that the cells in the sample are concentrated at the bottom of the cell carrying container due to the action of the sound waves. In this way, damage to the cells in the sample caused by large centrifugal force and high centrifugal speed can be avoided, cell concentration can be achieved without centrifugal force, it can adapt to most scenarios, improve the safety and integrity of the concentrated cells, while reducing the time and cost of cell concentration, and can maintain higher cell activity.

[0110] The above are only specific embodiments of the present application, but the scope of protection of the present application is not limited thereto. Any person skilled in the art can easily conceive of various equivalent modifications or substitutions within the technical scope disclosed in this application, and such modifications or substitutions should be included in the scope of protection of this application. Therefore, the scope of protection of this application should be based on the scope of protection of the claims.

Claims

1. A cell concentration device, characterized in that: include: A body, wherein the body is formed with a receiving groove, the receiving groove is used to place a cell-carrying container, and the cell-carrying container stores a sample to be concentrated; At least two transducers, the two transducers being respectively disposed on two sides of the containing tank, the transducers being attached to the cell-carrying container, and the transducers being configured to convert electrical signals into mechanical vibrations to generate sound waves; a container moving assembly, the container moving assembly being disposed on the body and being used to lift or lower the cell-carrying container; a control module, the control module being disposed on the body and connected to the transducer and the container moving assembly; Among them, the control module controls the two transducers to generate sound waves so that the two transducers simultaneously transmit the sound waves to the cell-carrying container; and at the same time controls the container moving component to lift the cell-carrying container so that the cells in the sample are concentrated at the bottom of the cell-carrying container due to the action of the sound waves.

2. The device according to claim 1, characterized in that The container moving component is also connected to the cell-carrying container; The control module is used to control the container moving component to rotate and rise, thereby driving the cell holding container to rotate and rise, so that the cells in the sample are concentrated at the bottom of the cell holding container due to the action of the sound waves.

3. The device according to claim 1, characterized in that The surface of the transducer that is in contact with the cell-carrying container is coated with a coupling agent.

4. The device according to claim 1, characterized in that The two transducers are symmetrically arranged on two side surfaces of the accommodating groove, and the working parameters of the two transducers are the same.

5. The device according to claim 4, characterized in that The operating parameters include at least frequency and excitation voltage. The frequency of the transducer is determined according to the node position of the sound wave and the sound wave radiation intensity. The excitation voltage is determined according to the particle size of the particles in the sample during concentration.

6. The device according to claim 5, characterized in that The frequency range of the transducer is 1 MHz-5 MHz; the excitation voltage range of the transducer is 30-120 V.

7. The device according to claim 1, characterized in that The sample liquid surface of the cell holding container is at least flush with the upper end of the transducer.

8. The device according to claim 1, characterized in that The cell-carrying container includes a centrifuge tube.

9. The device according to claim 8, characterized in that When the bottom of the centrifuge tube rises to a position flush with the middle of the transducer, the control module controls the container moving assembly to gradually reduce the rising speed of the cell-carrying container until the centrifuge tube stops rising.

10. The device according to claim 1, characterized in that The rotation speed and rising speed of the cell holding container are determined according to the size of the cell holding container.

11. The device according to any one of claims 1 to 10, characterized in that The transducer is a piezoelectric lead zirconate titanate transducer.

12. A method for controlling cell concentration, characterized in that: Applicable to a cell concentrating device according to any one of claims 1 to 11; the method comprising: placing a cell-carrying container containing a sample to be concentrated in a receiving tank of the cell concentrator; controlling the two transducers to simultaneously propagate sound waves toward the cell-carrying container; The container moving assembly is controlled to lift the cell holding container, so that the cells in the sample are concentrated at the bottom of the cell holding container due to the action of the sound waves.

13. The method according to claim 12, characterized in that The method further comprises: determining the frequency of the transducer according to the node positions and the radiation of the acoustic wave, and / or determining the excitation voltage of the transducer according to the particle size of the particles in the sample during concentration, and / or determining the rotation speed and the rising speed of the cell holding container according to the size of the cell holding container; controlling the transducer to convert the electrical signal into mechanical vibration according to the frequency and the excitation voltage to generate sound waves; The container moving assembly is controlled to lift the cell holding container at the ascending speed, and the container moving assembly is simultaneously controlled to rotate the cell holding container at the rotating speed, so that the cells in the sample are enriched at the bottom of the cell holding container due to the action of the sound waves.

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