Cell processing method, cell processing system, cell processing apparatus, and storage medium

Abstract

The invention discloses a cell processing method, a cell processing system, a cell processing device and a storage medium. A cell processing method for separating cells adhered to a culture surface of a culture container from the culture container by using a cell processing system including a vibration unit configured to generate vibration, the cell processing method including separating cells adhered to the culture surface of the culture container from the culture container in a state in which the vibration unit is in contact with a vibration transmitting material, the method includes heating the vibration-transmitting material by causing the vibration unit to vibrate in a first mode to increase a temperature of the vibration-transmitting material, and separating the cells from the culture vessel by causing the vibration unit to vibrate in a second mode different from the first mode after the heating is started in a state in which the vibration-transmitting material is in contact with the culture vessel.

Description

Technical Field

[0001] The present invention relates to a cell processing method, a cell processing system, a cell processing device and a computer-readable medium. Background Art

[0002] Cells produced by cell culture have been used in the field of drug development and regenerative medicine. In particular, in the case of a large number of adherent cells to be cultivated, after the adherent cells adhered to the culture container and the scaffold material are separated and collected from the culture container and the scaffold material, the adherent cells are moved to another culture container and cultivated again by passage operation. In addition, even if the passage operation is not performed, when the adherent cells are to be used, it is also desirable to separate the adherent cells from the culture container and the scaffold material. Because the temperature range that enables cells to have a high proliferation rate and / or a high survival rate varies according to the cell type, the cell culture process is usually performed by using a device (such as an incubator) maintained at a constant temperature. However, when an operation such as a cell separation operation is to be performed, the culture container must be taken out from the incubator. Therefore, there is the possibility that the cell temperature in the culture container placed outside the incubator becomes close to room temperature, and the survival rate of the cell may be reduced.

[0003] According to the technology discussed in Japanese Patent Application Laid-Open No. 2005-328726, a heater is arranged on a placement table on which a culture container taken out of a culture chamber is placed, so that a culture processing apparatus can maintain a culture medium in the culture container at a constant temperature. Summary of the invention

[0004] Some embodiments of the present invention are directed to providing a cell processing method capable of adjusting the temperature of a member in contact with a culture container within a desired range when cells attached to a culture surface of a culture container are to be separated. In addition, some embodiments of the present invention are directed to providing a cell processing system and a cell processing device capable of adjusting the temperature of a member in contact with a culture container within a desired range when cells attached to a culture surface of a culture container are to be separated.

[0005] The above-mentioned method can be realized by the present invention described below. That is, according to one aspect of the present invention, a cell processing method for separating cells adhered to a culture surface of a culture container from a culture container by using a cell processing system including a vibration unit configured to generate vibrations, the method comprising: in a state where the vibration unit is in contact with a vibration transfer material, heating the vibration transfer material by causing the vibration unit to vibrate in a first mode to increase the temperature of the vibration transfer material, and in a state where the vibration transfer material is in contact with the culture container, after heating starts, causing the vibration unit to vibrate in a second mode different from the first mode to separate the cells from the culture container.

[0006] According to another aspect of the present invention, a cell processing device is provided for separating cells adhered to a culture surface of a culture container from the culture container, the cell processing device comprising a vibration unit configured to generate vibrations and a control unit configured to control the vibrations generated by the vibration unit, wherein the control unit controls the vibration unit to vibrate in a first mode to transfer the vibrations to the vibration transfer material so as to increase the temperature of the vibration transfer material when the vibration unit is in contact with the vibration transfer material, and wherein the control unit controls the vibration unit to vibrate in a second mode different from the first mode to separate the cells from the culture container when the vibration transfer material is in contact with the culture container.

[0007] According to another aspect of the present invention, a cell processing system is provided for separating cells adhered to a culture surface of a culture container from the culture container, the cell processing system comprising a vibration unit configured to generate vibrations and a control unit configured to control the vibrations generated by the vibration unit, wherein the control unit controls the vibration unit to vibrate in a first mode to transmit the vibrations to the vibration transfer material so as to increase the temperature of the vibration transfer material when the vibration unit is in contact with the vibration transfer material, and wherein the control unit controls the vibration unit to vibrate in a second mode different from the first mode to separate the cells from the culture container when the vibration transfer material is in contact with the culture container.

[0008] Further features of the present invention will become apparent from the following description of exemplary embodiments with reference to the attached drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0009] Figure 1 is a schematic diagram showing a device configuration of a cell processing system according to a first exemplary embodiment.

[0010] Figure 2 is a flowchart illustrating a cell processing method according to a first exemplary embodiment.

[0011] Figure 3 is an exemplary diagram of a cell processing method according to the first exemplary embodiment.

[0012] Figure 4A and Figure 4B is a schematic cross-sectional view showing a cell processing system according to a first exemplary embodiment.

[0013] Figure 5 is a conceptual diagram illustrating heat generation according to the first exemplary embodiment.

[0014] Fig. 6A and Figure 6B is a schematic diagram illustrating vibration modes according to the first exemplary embodiment.

[0015] Figure 7 is a schematic diagram showing temperature changes according to the first exemplary embodiment.

[0016] Figure 8 is a schematic diagram illustrating local vibration according to the second exemplary embodiment.

[0017] 9A to 9C is a schematic diagram illustrating a vibration mode according to the second exemplary embodiment.

[0018] Fig. 10A and Fig. 10B : is a schematic diagram showing an example of changing the vibration pattern according to the second exemplary embodiment.

[0019] Fig.11 is a schematic diagram showing a configuration example of a cell processing apparatus according to a third exemplary embodiment.

[0020] Fig.12 is a schematic diagram showing a device configuration of a cell processing system according to a third exemplary embodiment.

[0021] Fig.13 is a flowchart illustrating a cell processing method according to a third exemplary embodiment.

[0022] Fig.14 is a flowchart illustrating a cell processing method according to a first exemplary embodiment. DETAILED DESCRIPTION

[0023] Japanese Patent Application Publication No. 2005-328726 does not discuss the type of heater and the heat transfer path from the heater to the culture container. If the culture container is simply placed on a placement table with a heater, it takes time for the heat to be transferred from the heater to the culture container. Therefore, there is a possibility that the cell temperature cannot be sufficiently maintained.

[0024] The inventors of the present invention studied a method for maintaining the temperature of cells when cells are separated from a culture container and found that if a commonly used heater is simply arranged in the housing of a cell processing device, the temperature of the vibration transmission material in which the culture container is placed may not be sufficiently increased because it takes time to increase the temperature of the heater.

[0025] The inventors conducted further research based on the above knowledge and found that the vibration transfer material can be heated by applying vibration to the vibration transfer material before placing the culture container. It was also found that the temperature of the vibration transfer material can be increased more quickly by directly heating the vibration transfer material with the vibration of the vibration transfer material than by driving the heater alone.

[0026] Hereinafter, the present invention will be described in further detail exemplary embodiments.

[0027] In the cell processing method according to the present exemplary embodiment, the cells adhering to the culture surface of the culture container are separated by transmitting the vibration generated by the vibration unit for generating vibration included in the cell processing system to the culture container via the vibration transmission material. In addition, in the cell processing method according to the present exemplary embodiment, in order to adjust the temperature of the cells contained in the culture container, before the culture container contacts the vibration transmission material, the vibration unit is pre-vibrated in a mode of increasing the temperature of the vibration transmission material. In this way, when the culture container is moved from a culture environment such as an incubator to the cell processing system, the temperature of the cells contained in the culture container can be managed.

[0028] (Cell Processing System)

[0029] Figure 1 1 is a schematic diagram showing the device configuration of the cell processing system according to the present exemplary embodiment. The cell processing system according to the present exemplary embodiment includes at least a vibration unit for generating vibration and a control unit for controlling the vibration generated by the vibration unit. The cell processing system 10 separates the cells 3 adhered to the culture surface of the culture container 100 from the culture surface by transmitting the vibration generated by the vibration unit to the cells 3 via a vibration transmitting material (not shown). In the cell separation process, the culture container 100 is placed and pressed by the weight of the dish weight 110. Figure 1 The control circuit shown is an example of a control unit. The control circuit controls the vibration generated by the vibration unit. The control unit may include a module executed by a central processing unit (CPU) or a microprocessing unit (MPU), or may include a circuit that performs a specific function, such as an application-specific integrated circuit (ASIC). The temperature sensor 118 is arranged in clamping contact with the vibration bucket 107. The temperature sensor 118 is an example of a measuring unit. The temperature sensor 118 can be fixed by any fixing method, such as bonding. This configuration enables direct or indirect temperature measurement of the culture surface of the culture container 100. For the purpose of temperature control, water pipes 105a and 105b are arranged around the vibration bucket 107 for cooling. For example, the water pipe 105a side is set to the inflow side of water (such as refrigerant), and the water pipe 105b side is set to the outflow side of water. The storage barrel 108 is arranged next to the vibration bucket 107 in the form of a groove, so that the vibration transfer fluid can move freely between the two barrels through the fluid path 111. The weight 103 is arranged to allow the vibration transfer fluid to move from the vibration bucket 107 to the storage bucket 108 and vice versa through the fluid path 111.

[0030] Furthermore, the present invention can be implemented by a cell processing system to which a plurality of devices and arithmetic means are connected, and the present invention also includes a cell processing apparatus configured by a single device for performing similar functions.

[0031] (Vibration unit)

[0032] Figure 4A and Figure 4B is a schematic cross-sectional view showing a cell processing system according to the present exemplary embodiment. Figure 4A The state of the culture container 100 before contacting the cell processing system is shown. Figure 4A and Figure 4B The vibration unit 107 shown in each of the figures is a piezoelectric vibration unit. The vibration unit 107 includes a vibration plate 102 and a vibrator 117 adhered to each other. When a driving voltage is applied to a piezoelectric material included in the vibrator 117, the vibrator 117 expands and contracts to vibrate. When the vibrator 117 expands and contracts to vibrate, the vibration plate 102 performs an extension / displacement motion, i.e., a bending / deformation motion. As a result, the vibration unit 107 vibrates to generate elastic waves.

[0033] The vibration unit 107 may be a device capable of generating vibrations, such as a piezoelectric device or a motor. In particular, in order to separate cells from the culture container 100, it is preferred to use a device capable of generating ultrasonic band vibrations as the vibration unit 107. The vibrator 117 used for the vibration unit 107 may be a piezoelectric type or an electromagnetic type, as long as a constant frequency vibration can be generated thereby. In order to accurately control the vibration waveform and the vibration frequency, the vibrator 117 may be a piezoelectric vibrator. The piezoelectric vibrator may be selected from a single piezoelectric crystal type, a bimorph type, and a bolt-fastened Langevin type.

[0034] (case)

[0035] The cell processing system further comprises a housing 101 for holding a vibration unit 107. Figure 4A and Figure 4B As shown, the housing 101 may have a bank-like protrusion on the upper side of the vibration unit 107 so as to maintain the vibration transfer material when the cell processing system is placed on a laboratory bench. In addition, a heater for increasing the temperature of the entire housing 101 and maintaining its equilibrium state may be arranged in the housing 101. Through the temperature management of the heater for maintaining the temperature of the entire housing 101 and the vibration unit 107 for increasing the temperature of the vibration transfer material, the temperature can be quickly and efficiently adjusted when performing cell processing.

[0036] (Vibration Transmitting Material)

[0037] When the cell treatment system is used, the vibration transmission material 129 is placed so as to contact the vibration unit 107. The vibration transmission material 129 may be a material capable of transmitting at least a portion of the vibration generated by the vibration unit 107 from the vibration unit 107 to the culture container 100. In terms of transmission capability, it is preferred that the vibration transmission material 129 may be a liquid or a solid. More preferably, the vibration transmission material 129 may contain water or silicone rubber. By vibrating the vibration unit 107 in a state where the vibration transmission material 129 is in contact with both the vibration unit 107 and the culture container 100, vibration can be effectively applied to the cells.

[0038] (Cultivation Container)

[0039] Any container that can be used to culture cells can be used as the culture container 100 described in this exemplary embodiment. In addition, a culture container that stores a scaffold material (such as a microcarrier or a hollow fiber material) inside can also be used as the culture container 100. Examples of the culture container 100 include a dish, a flask, a well plate, and a culture bag.

[0040] A material capable of transmitting vibration or a material capable of deforming according to vibration can be used as the material of the culture container 100. For example, the culture container 100 can be made of a polymer material such as polystyrene or a metal material. The culture container 100 is placed in contact with the vibration transmitting material 129 placed on the vibration unit 107. In order to effectively perform cell separation, when viewed from the culture surface to which the cells in the culture container 100 adhere, it is preferred that the surface where the vibration transmitting material 129 contacts the culture container 100 is located outside the culture container 100.

[0041] (cell)

[0042] The cell processing method according to this exemplary embodiment can be applied to various types of cells. For example, various types of cells include cells derived from Chinese hamster ovary (CHO cells), mouse connective tissue L929 cells, mouse skeletal muscle myoblasts (C2C12 cells), normal double fibroblasts derived from human fetal lung (TIG-3 cells), cells derived from human fetal kidney (HEK 293 cells), cells derived from human alveolar basal epithelial adenocarcinoma (A549 cells), cells derived from human cervical cancer (HeLa cells), epithelial cells, endothelial cells, skeletal muscle cells, smooth muscle cells, cardiomyocytes, neuronal cells, glial cells, fibroblasts, hepatic parenchymal cells, hepatic non-parenchymal cells, adipocytes, induced pluripotent stem (iPS) cells, embryonic stem (ES) cells, embryonic germ (EG) cells, embryonic carcinoma (EC) cells, mesenchymal stem cells, liver stem cells, pancreatic stem cells, skin stem cells, muscle stem cells, germ stem cells, progenitor cells of various tissues, and at least one selected from a group of cells differentiated and induced by these cells.

[0043] (Vibration Mode)

[0044] Fig. 6A and Figure 6B 1 is a schematic diagram showing vibration modes according to the present exemplary embodiment. In the present exemplary embodiment, the vibration unit 107 vibrates in at least two modes, namely, a first mode for increasing the temperature of the vibration transfer material 129 and a second mode for separating cells from the culture container 100 .

[0045] In order to effectively perform temperature management and cell separation, preferably, the vibrations generated in the first and second modes are vibrations of the ultrasonic band. In addition, by making the frequency of the first mode (heating vibration) higher than the frequency of the second mode (separation vibration), temperature management can be performed more quickly. For example, the second mode may be a vibration whose frequency is swept from 20kHz to 200kHz. By using a frequency sweep, a vibration of a resonant frequency can be generated, and a vibration with a large amplitude can be obtained. In addition, for example, the first mode may be a vibration with a fixed frequency falling within the range of 100kHz to 200kHz. By using a vibration with a relatively high and fixed frequency, the vibration transfer material 129 can be heated more quickly.

[0046] (Process flow of cell treatment method)

[0047] Figure 2 1 is a flowchart showing a process flow of the cell processing method according to the present exemplary embodiment. First, in the preparation process, the user prepares the vibration unit 107 and the vibration transfer material 129 in a state where the vibration transfer material 129 is placed to contact the vibration unit 107 of the cell processing system (S201). In addition, the vibration transfer material 129 may be placed and fixed to the vibration unit 107 in advance. The preparation of the vibration unit 107 and the vibration transfer material 129 may be automatically performed by an optional system.

[0048] Next, the user inputs a preheating instruction to the cell processing system through the input unit. According to the instruction, during the heating process (S202), the control unit of the cell processing system instructs the vibration unit 107 to drive the vibration unit 107 so that the vibration unit 107 starts to vibrate in the first mode. Figure 2 As shown, during the heating process, the vibration unit 107 vibrates the vibration transfer material 129 by vibrating in the first mode, thereby increasing the temperature of the vibration transfer material 129. Figure 5 The conceptual diagram in exemplifies the generation of heat. When the elastic wave generated by the vibration unit 107 is transmitted to the vibration transmission material 129, the temperature of the vibration transmission material 129 increases due to frictional heat caused by friction between molecules.

[0049] The temperature of the vibration transmission material 129 is preferably set to a temperature suitable for the type of cells to be separated to survive. Suitable temperatures vary depending on the cell type. However, for example, the temperature of the vibration transmission material 129 can be set to 37°C.

[0050] In addition, the instruction to perform preheating does not always have to be issued by the user, and the instruction may be automatically executed by the cell processing system. In addition, the user may use an input unit such as a button, a touch panel, a keyboard, a mouse, or a controller. Fig.14 As shown in the flowchart in , if the heater is disposed on the housing 101, when the vibration unit 107 is activated according to an instruction to perform preheating, the heater may be activated (S1402).

[0051] Figure 7 1 is a schematic diagram showing the temperature change during the heating process. For example, in the case where the heater is arranged on the housing 101, the temperature of the vibration transfer material 129 gradually increases according to the increase in the heater temperature after the heater is activated, but it takes some time before the temperature reaches the equilibrium temperature. Therefore, the heating process using the vibration of the first mode is performed simultaneously with the activation of the heater. In this way, the temperature of the vibration transfer material 129 can be increased more rapidly.

[0052] Here, the cell processing system may further include a measuring unit and a notification unit. When the heating process is finished, that is, when the temperature of the vibration transfer material 129 reaches a predetermined temperature, a notification unit (not shown) may issue a notification to the surroundings (S203). The notification unit may issue a notification by using at least any one of light, sound, and character display. The temperature of the vibration transfer material 129 is measured by a measuring unit (e.g., a temperature sensor 118). The notification unit issues a notification that preheating is completed, whereby the user can easily understand when the placement process is performed, thereby being able to perform the operation efficiently.

[0053] Next, in the placement process performed after the start of the heating process, the culture container 100 is placed so as to contact the vibration transmission material 129 (S204). The cells 3 held on the culture surface of the culture container 100 are cultured in the culture process (S208). Through the placement process, the vibration unit 107, the vibration transmission material 129, and the culture container 100 are placed in this order. The placement process can be performed manually or automatically.

[0054] In the separation process (S205) performed after the placement process, the control unit vibrates the vibration unit 107 in the second mode. In other words, the vibration unit 107 vibrates in the second mode in a state where the vibration transmission material 129 is in contact with the culture container 100. By this vibration, the cells in the culture container 100 are vibrated and separated from the culture surface of the culture container 100.

[0055] In the present exemplary embodiment, an example of the vibration pattern according to the present invention is described.

[0056] (First Mode)

[0057] In the first mode for increasing the temperature of the vibration transfer material 129 , it is preferred that the vibration has a maximum amplitude at a plurality of different positions on the vibration surface of the vibration unit 107 in order to rapidly increase the temperature of the vibration transfer material 129 . Figure 8 1 is a diagram showing local vibrations on the vibration surface (vibration plate 102) of the vibration unit 107, which have maximum amplitudes at multiple locations. When the vibration plate 102 vibrates in a mode that generates multiple local vibrations, the shape of the vibration transmission material 129 in contact with the vibration plate 102 changes significantly, so that the temperature of the vibration transmission material 129 can be rapidly increased.

[0058] (Second Mode)

[0059] 9A to 9C is a schematic diagram showing vibration modes.

[0060] like Fig. 9C As shown, the first mode and the second mode may be performed simultaneously in the separation process. In other words, the second mode performed in the separation process may be a combination of a plurality of vibration modes. By including a second mode of vibration having a frequency higher than the vibration frequency in the first mode, the temperature of the vibration transfer material 129 may be effectively increased. In addition, the vibration in the second mode may be Fig.9A The rectangular wave shown or Fig. 9B The triangle wave shown.

[0061] By generating vibration in the second mode after the culture container 100 is placed, the temperature of the vibration transmission material 129 can also be increased. Therefore, the temperature of the cells can be adjusted.

[0062] (Switch between vibration modes)

[0063] Fig. 10A and Fig. 10B is a diagram showing an example of switching between vibration modes. Fig. 10B As shown, even in the case where the temperature drop of the vibration transfer material 129 cannot be prevented by applying vibration alone in the second vibration mode, the temperature can be raised again by performing the heating process after the separation process starts.

[0064] Furthermore, in the case where the temperature of the vibration transfer material 129 measured by the measuring unit (not shown) during the heating treatment falls outside a predetermined range, it is preferred that the control unit changes the vibration frequency or amplitude of the vibration unit 107. By changing the vibration frequency or amplitude, the vibration transfer material 129 can be maintained at a temperature suitable for cell survival. For example, in the case where the temperature of the vibration transfer material 129 is to be maintained at 37°C, it is effective to perform control to reduce the amplitude when the measured temperature is 39°C and control to increase the amplitude when the measured temperature is 35°C. Furthermore, the target of the temperature measured by the measuring unit is not limited to the vibration transfer material 129, and the measuring unit can also measure the temperature of a part of the vibration unit 107.

[0065] (Configuration example of cell processing device)

[0066] Fig.11 1 is a schematic diagram showing a configuration example of the cell processing apparatus 1 according to the present exemplary embodiment. The housing 101 of the cell processing apparatus may include a power button 126, a detach button 127, and a completion button 128. By arranging the above-mentioned buttons, the user can use the cell processing apparatus by simply operating the buttons arranged on the cell processing apparatus. Therefore, a space-saving cell processing apparatus that is easy to use can be provided.

[0067] like Figure 3 As shown, the user operates a button such as the power button 126 to use the cell processing device through the following process. When the user presses the power button 126, the heater that heats the housing 101 with a constant input is turned on, and the vibration unit 107 starts to generate heating vibration (vibration in the first mode). Thereafter, when the preset heating time has passed, the vibration unit 107 stops generating the heating vibration. At this time, the heat-retaining heater remains in the energized state.

[0068] Next, the user places the culture container 100 taken out of the incubator on the cell processing device and presses the separation button 127 to start the separation vibration (vibration in the second mode). After the user visually confirms the separation of the cells, the user presses the completion button 128 to stop the separation vibration.

[0069] In the case where the user continuously performs cell separation on a plurality of culture containers 100, the user places the second and subsequent culture containers 100 on the cell processing device immediately after the processing of the first culture container 100 is completed. Then, the user presses the separation button 127 after placing the culture container 100 and presses the completion button 128 after confirming the cell separation, and repeats the operation. When the user separates cells from all the culture containers 100, the user presses the power button 126 again to turn off the power and stop the heat preservation heater.

[0070] (Example of temperature adjustment mechanism)

[0071] Fig.12 is a schematic diagram showing the device configuration of the cell processing system according to this exemplary embodiment. In order to prevent the temperature of the cells from rising rapidly or being too high, in some embodiments, such as Fig.12 A temperature regulating mechanism is provided as shown. A cooling space 135 is arranged on the lower side of the vibration unit 107, that is, on the side opposite to the side where the culture container 100 is placed. The culture container 100 holds the cells 3 and the culture medium 8. The cooling space 135 is covered by a wall-shaped heat insulating member 132 in contact with the housing 101. The cooling space 135 is also divided by a cooling device 134, which includes a cooling plate 130, a cooler 131, a cooling fin 104 and a cooling fan 133. The cooling plate 130 is arranged on the lower side and has excellent thermal conductivity. The cooling plate 130 is against the cooler 131 such as a Peltier element, and the cooling fin 104 is arranged on the side where heat is discharged. A cooling fan 133 for blowing out waste heat is arranged on the lower side of the cooling fin 104. By providing the above-mentioned temperature regulating mechanism, the temperature of the cells can be managed with higher accuracy.

[0072] (Example of a cell processing system with a storage unit)

[0073] The cell processing system according to the present exemplary embodiment may have a storage unit. The storage unit may be configured by a storage medium such as an optional memory or an optical disk. Fig.13 2 is a flowchart showing a cell processing method according to the present exemplary embodiment. The storage unit stores processing conditions associated with at least any one of cell types, cell culture conditions, and the type of the culture container 100 .

[0074] The processing conditions include at least any one of temperature, vibration frequency and driving voltage. The control unit refers to the processing conditions associated with the identification information (ID) information stored in the storage unit, and controls the vibration generated by the vibration unit 107 based on the identification information of the culture container 100 or the cell as the processing target (S1302). The identification information of the processing target can be optically read and obtained from the barcode, can be manually input by the user, or can be selected by the user from a list. Through the above configuration, cell separation can be performed according to different states of each sample.

[0075] (Cell treatment method implementation procedure)

[0076] Some embodiments may be implemented by performing the following processing. In other words, some embodiments of the present invention may be implemented by providing a system or device via a network or storage medium with software (program) for implementing one or more functions according to the various exemplary embodiments described above. Some embodiments of the present invention may also be implemented by a computer (or CPU or microprocessing unit (MPU)) of a system or device reading and executing a program. A computer includes one or more processors or circuits, and may also include a network of multiple independent computers, independent processors or circuits to read and execute computer executable instructions.

[0077] In this case, the processor or circuit may include a central processing unit (CPU), a microprocessing unit (MPU), and a graphics processing unit (GPU). The processor or circuit may also include an application-specific integrated circuit (ASIC) or a field-programmable gate array (FPGA). In addition, the processor or circuit may include a digital signal processor (DSP), a data stream processor (DFP), or a neural processing unit (NPU).

[0078] According to the present invention, a cell processing method can be provided, which can adjust the temperature of a member in contact with a culture container to a desired range when cells adhered to a culture surface of a culture container are to be separated therefrom. In addition, according to the present invention, a cell processing device and a cell processing system can be provided, which can adjust the temperature of a member in contact with a culture container to a desired range when cells adhered to a culture surface of a culture container are to be separated therefrom.

[0079] Although exemplary embodiments have been described, it is to be understood that some embodiments are not limited to the disclosed exemplary embodiments.The scope of the following claims is to be accorded the broadest interpretation so as to encompass all such modifications, equivalent structures and functions.

Claims

1. A cell processing method for separating cells adhered to a culture surface of a culture container from the culture container by using a cell processing system including a vibration unit configured to generate vibration, the cell processing method comprising: heating the vibration transfer material by vibrating the vibration unit in a first mode to increase the temperature of the vibration transfer material in a state where the vibration unit is in contact with the vibration transfer material; and In a state where the vibration transmitting material is in contact with the culture container, after the heating starts, the cells are separated from the culture container by vibrating the vibration unit in a second mode different from the first mode.

2. The cell treatment method according to claim 1, wherein: The vibrations in the first mode and the second mode are vibrations of an ultrasonic band.

3. The cell treatment method according to claim 1, wherein: The vibration in the first mode is a vibration having a frequency higher than that in the second mode.

4. The cell treatment method according to claim 1, wherein: The vibration unit includes a vibrator including a piezoelectric material and a vibration plate, and generates vibrations of a first mode and a second mode due to a driving voltage applied to the vibrator.

5. The cell treatment method according to claim 1, wherein: The vibration in the first mode is a vibration having a maximum amplitude at a plurality of different positions on the vibration surface of the vibration unit.

6. The cell treatment method according to claim 1, wherein: The cell processing method includes at least a time period of performing heating and separation simultaneously.

7. The cell treatment method according to claim 1, wherein: After the separation is started, the vibration unit generates vibration in the first mode.

8. The cell treatment method according to claim 1, wherein: The vibration in the second mode is a rectangular wave or a triangular wave.

9. The cell treatment method according to claim 1, wherein: In at least any one of the heating and the separating, in a case where the temperature of the vibration transmission material falls outside a predetermined range, a vibration frequency or amplitude of the vibration unit is changed.

10. The cell treatment method according to claim 1, wherein: The vibration transmitting material is solid or liquid.

11. The cell treatment method according to claim 10, wherein: The vibration transmitting material includes silicone rubber or water.

12. A non-volatile computer-readable medium storing instructions which, when executed by a computer, cause the computer to execute a cell processing method for separating cells adhered to a culture surface of a culture container from the culture container by using a cell processing system including a vibration unit configured to generate vibrations, the cell processing method comprising: heating the vibration transfer material by vibrating the vibration unit in a first mode to increase the temperature of the vibration transfer material in a state where the vibration unit is in contact with the vibration transfer material; and In a state where the vibration transmitting material is in contact with the culture container, after the heating starts, the cells are separated from the culture container by vibrating the vibration unit in a second mode different from the first mode.

13. A cell processing device for separating cells adhered to a culture surface of a culture container from the culture container, the cell processing device comprising: a vibration unit configured to generate vibration; as well as a control unit configured to control the vibration generated by the vibration unit, wherein the control unit controls the vibration unit to vibrate in a first mode when the vibration unit is in contact with the vibration transfer material, so as to transfer the vibration to the vibration transfer material to increase the temperature of the vibration transfer material; and Wherein, the control unit separates the cells from the culture container by controlling the vibration unit to vibrate in a second mode different from the first mode when the vibration transfer material is in contact with the culture container.

14. The cell processing device according to claim 13, wherein: The vibration in the first mode is a vibration having a frequency higher than that in the second mode.

15. The cell processing apparatus according to claim 13, further comprising a storage unit configured to store a processing condition associated with at least any one of a cell type of the cell, a culture condition of the cell, and a type of a culture container, in, The control unit controls vibration generated by the vibration unit according to the processing condition.

16. The cell processing device according to claim 13, further comprising: a measuring unit configured to measure a temperature of the vibration transmitting material; as well as A notification unit configured to issue a notification by using at least any one of light, sound, and character display when the temperature measured by the measurement unit reaches a predetermined temperature.

17. A cell processing system for separating cells adhered to a culture surface of a culture container from the culture container, the cell processing system comprising: a vibration unit configured to generate vibration; as well as a control unit configured to control the vibration generated by the vibration unit, wherein the control unit controls the vibration unit to vibrate in a first mode when the vibration unit is in contact with the vibration transfer material, so as to transfer the vibration to the vibration transfer material to increase the temperature of the vibration transfer material; and Wherein, the control unit separates the cells from the culture container by controlling the vibration unit to vibrate in a second mode different from the first mode when the vibration transfer material is in contact with the culture container.

18. The cell processing system according to claim 17, wherein: The vibration in the first mode is a vibration having a frequency higher than that in the second mode.

19. The cell processing system according to claim 17, further comprising a storage unit configured to store processing conditions related to at least any one of a cell type of the cell, a culture condition of the cell, and a type of a culture container, in, The control unit controls vibration generated by the vibration unit according to the processing condition.

20. The cell processing system of claim 17, further comprising: a measuring unit configured to measure a temperature of the vibration transmitting material; as well as A notification unit configured to issue a notification by using at least any one of light, sound, and character display when the temperature measured by the measurement unit reaches a predetermined temperature.

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