Cell stripping equipment

Abstract

Provided is a cell detachment apparatus that separates cells attached to a culture surface from a culture surface of a culture substrate by applying vibration to the culture surface, the cell detachment apparatus comprising: a vibration unit that includes a vibrator that generates vibration; and a first holding unit that holds the culture substrate in such a manner that the position of the culture substrate in the horizontal direction with respect to the vibrator is allowed to be changed.

Description

Technical Field

[0001] The present invention relates to a cell detachment device. Background Art

[0002] For the purpose of treatment and research and development in the medical field, cells can be cultured and used on a culture plate or at the bottom of a container such as a culture dish (petri dish). However, adherent cells are attached to the bottom of the container. Therefore, it is necessary to separate and remove the adherent cells from the culture container.

[0003] Japanese Patent Application Laid-Open No. 2008-092857 describes a cell detachment apparatus including a separator that separates desired living cells among a living cell group from a wall surface of a container by applying ultrasonic waves.

[0004] Japanese Patent Application Laid-Open No. 2015-043751 describes a vibration device that removes bubbles generated during culture by vibrating a culture container. Summary of the invention

[0005] Some inconveniences have been found in the cell detachment apparatus of Japanese Patent Application Laid-Open No. 2008-092857 and the vibration apparatus of Japanese Patent Application Laid-Open No. 2015-043751. In other words, the cell detachment apparatus of Japanese Patent Application Laid-Open No. 2008-092857 does not have a structure for fixing the container, so the position of the container varies due to the vibration generated by applying ultrasonic waves, and as a result, the cells may not be separated.

[0006] The vibration device of Japanese Patent Publication No. 2015-043751 describes a structure for holding a culture container by applying force to the culture container in a vertical direction in order to hold the culture container. However, according to research, the appropriate position for applying vibration varies with the structure. In other words, when vibration is continuously applied, the peak position of the amplitude may change, and when the vibration mode changes, the peak position of the amplitude may change. As a result, in the case where the structure keeps the position of the culture container only at a certain specific position, it may be difficult to separate cells or the survival rate may be reduced due to cell damage.

[0007] Therefore, the present disclosure provides a cell detachment apparatus which solves the above inconvenience by not only maintaining the position of a culture container for cells but also allowing the position to be changed.

[0008] One aspect of the present disclosure provides a cell detachment device that separates cells attached to a culture surface from the culture surface by applying vibration to the culture surface of the culture substrate, the cell detachment device comprising: a vibration unit including a vibrator that generates the vibration; and a first holding unit that holds the culture substrate in a manner that allows the position of the culture substrate relative to the vibrator in a horizontal direction to be changed.

[0009] Further features of the present disclosure will become apparent from the following description of exemplary embodiments with reference to the attached drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0010] Figure 1 is a diagram showing a cell detachment apparatus according to an embodiment of the present disclosure.

[0011] FIG. 2A to FIG. 2C is a diagram showing a cell detachment apparatus according to a first embodiment of the present disclosure.

[0012] FIG. 3A to FIG. 3E is a diagram showing a cell detachment apparatus according to a second embodiment of the present disclosure.

[0013] FIG. 4A to FIG. 4E is a diagram showing a cell detachment apparatus according to a third embodiment of the present disclosure.

[0014] Figure 5 is a diagram showing a cell detachment apparatus according to a fourth embodiment of the present disclosure.

[0015] FIG. 6A to FIG. 6C is a diagram showing a cell detachment apparatus according to a fifth embodiment of the present disclosure.

[0016] 7A to 7D is a diagram showing an example of a weight in a cell detachment apparatus according to a sixth embodiment of the present disclosure.

[0017] FIG. 8A to FIG. 8D is a diagram showing a cell detachment apparatus according to a seventh embodiment of the present disclosure.

[0018] Fig. 9 is a diagram showing a cell detachment apparatus according to an eighth embodiment of the present disclosure.

[0019] Fig.10 is a diagram showing a cell detachment apparatus according to a ninth embodiment of the present disclosure.

[0020] FIG. 11A to FIG. 11D is a diagram showing a cell detachment apparatus according to a tenth embodiment of the present disclosure.

[0021] Fig.12 is a diagram showing a cell detachment apparatus according to an eleventh embodiment of the present disclosure. DETAILED DESCRIPTION

[0022] Will refer to Figure 1 A cell detachment apparatus according to an embodiment of the present disclosure is described; however, the present disclosure is not limited thereto. Figure 1 is a schematic cross-sectional view of the cell detachment device according to the present embodiment.

[0023] The cell detachment device 100 according to the present embodiment is a cell detachment device 100 that detaches cells 3 attached to the culture surface from the culture surface by applying vibration to the culture surface of the culture substrate 8. The cell detachment device 100 includes a vibration unit 10 including a vibrator 16 that generates vibrations and a first holding unit 1 that holds the culture substrate 8 in a manner that allows the position of the culture substrate 8 relative to the vibrator 16 in the horizontal direction to be changed. Figure 1 In the example, the horizontal direction is the plane direction defined by the X-axis and the Y-axis, and the vertical direction is the Z-axis direction. The same applies to Figure 2A and cross-sectional views of subsequent figures.

[0024] Here, the phrase "holding the culture substrate 8 in a manner that allows the position of the culture substrate 8 in the horizontal direction to be changed" means that the position of the culture substrate 8 is allowed to be changed without applying vibration, and after the position change is completed, the culture substrate 8 can be held (fixed) in a manner that does not change the position of the culture substrate 8. By generating vibration using the vibrator 16 in a state where the culture substrate 8 is held, appropriate vibration is applied to the culture substrate 8 and the cells 3 attached to the culture surface of the culture substrate 8.

[0025] The first holding unit 1 in the present embodiment allows the position of the culture substrate 8 in the horizontal direction to be changed, so that the culture substrate 8 can be installed on the vibration unit 10 or at a selected position above the vibration unit 10. For example, in the case of a position where the amplitude of vibration generated by the vibrator 6 and transmitted to the culture substrate 8 changes the most, the culture substrate 8 can be changed to an appropriate position where the detachment rate and the survival rate of the cells 3 are increased by the first holding unit 1.

[0026] The cell detachment device 100 according to the present embodiment may include a second holding unit 2 that holds the position of the culture substrate 8 in the vertical direction. The second holding unit 2 may be a weight (loading unit) or a pressure applying unit that applies pressure so that the distance between the culture substrate 8 and the vibrator 16 is reduced. The weight may be configured to include a plurality of weights. Figure 1 As shown, the counterweight may be held by the first holding unit 1 or may be suspended from the first holding unit 1. Figure 1 As shown, the second holding unit 2 may have an engaging portion 11 for engaging with the culture substrate 8. Since the second holding unit 2 has the engaging portion 11, it is easy to maintain the position of the culture substrate 8. As described later, the first holding unit 1 in this embodiment may include a rotating mechanism that can rotate around an axis that is consistent with the direction perpendicular to the vibration surface of the vibrator 16. The rotating mechanism may include a vibration actuator that rotates the screw.

[0027] The cell detachment apparatus 100 according to the present embodiment may include a position control unit 14 that controls the horizontal position of the culture substrate 8. The position control unit 14 is connected to the stage 4 that allows the horizontal position of the culture substrate 8 to be moved in the XY direction, and is capable of controlling the movement. The position control unit 14 may be configured to control the rotation of the first holding unit 1 using a rotation mechanism.

[0028] The first holding unit 1 can be configured to be displaceable in the vertical direction. Since the first holding unit 1 is configured to be displaceable in the vertical direction, the first holding unit 1 can be retracted in the Z direction, or can be retracted in the Z direction and then retracted in the X or Y direction, so it is easy to install and remove the culture substrate 8.

[0029] The culture substrate 8 in this embodiment may include a container 7 and a cover 6. The container 7 has an opening and a culture surface for the cells 3, and the cover 6 covers the opening. Figure 1 As shown, the first holding unit 1 may be configured to hold a lid 6 , or may be configured to hold a container 7 .

[0030] The cell detachment device 100 according to the present embodiment may have an acoustic transmission medium 9 between the vibration unit 10 and the culture substrate 8. The acoustic transmission medium 9 is arranged in the path through which vibration, particularly vibration in the ultrasonic band, passes from the vibration unit 10 to the culture substrate 8, so that an air layer that causes vibration attenuation is not interposed. The acoustic transmission medium 9 may be a solid like silicone rubber, or may be a liquid like water. Alternatively, the acoustic transmission medium 9 may be a liquid, and the first holding unit 1 may be configured so that the culture substrate 8 is in contact with the acoustic transmission medium 9 and the culture substrate 8 is not in contact with the vibration unit 10.

[0031] The vibration unit 10 in the present embodiment may further include a vibration plate 15 for transmitting vibration generated in the vibrator 16, in addition to the vibrator 16. The vibration generated by the vibrator 16 may be vibration in an ultrasonic wave band.

[0032] Hereinafter, an example of the cell detachment apparatus 100 according to an embodiment of the present disclosure will be described.

[0033] First embodiment

[0034] Will refer to Figure 2A As Figure 2C An example of the cell detachment apparatus 100 according to the first embodiment of the present disclosure is described.

[0035] The cell detachment device 100 according to the present embodiment separates the cells 3 from the culture substrate 8 by applying vibrations in the ultrasonic wave band (hereinafter, it may be simply referred to as ultrasonic vibrations) to the cells 3 arranged on the culture substrate 8 and cultured. The cell detachment device 100 includes a disc-shaped vibration unit 10, which is constructed to include a piezoelectric element (vibrator) 16 fixed to a vibration plate 15 (not shown). An electrode (not shown) for giving an alternating signal is provided on the piezoelectric element 16, and the bottom plate 12 supports the vibration unit 10. Electrodes (not shown) are provided on the piezoelectric element 16 in such a manner that the front and back sides have opposite polarities to cause stretching vibrations, and a return electrode is also provided on the front side so as to be connected to the back electrode on the front side. By giving an alternating signal to the piezoelectric material, ultrasonic vibrations can be excited and applied.

[0036] In the cell detachment apparatus 100 according to the present embodiment, ultrasonic vibration is transmitted from the vibration plate 15 of the disk-shaped vibration unit 10 and applied to the culture substrate 8; however, Figure 2B As shown, the surface of the culture substrate 8 and the surface of the vibration plate 15 are not necessarily flat and may have a slight warpage. In this case, it may be difficult to transmit vibration. In order to make the bottom of the container 7 contact with the vibration plate 15 uniformly, as shown in FIG. Figure 2C As shown, by matching the center of gravity of the counterweight (second holding unit) 2 with the center of figure of the culture substrate 8, the counterweight 2 is loaded on the culture substrate 8 with good balance. When there is a gap between the vibration unit 10 and the culture substrate 8, the ultrasonic vibration is attenuated in the gap and the necessary vibration cannot be obtained, so it is necessary to load appropriately using the counterweight 2. On the other hand, when the counterweight 2 is too heavy, the vibration of the vibration unit 10 may be impaired, so the loading suitable for the container 7 can be selected.

[0037] Here, when ultrasonic vibration is applied to the culture substrate 8, the culture substrate 8 can float a trace of less than or equal to 10 μm together with the weight 2 when the ultrasonic vibration applies pressure, and the position becomes uncertain and shifts from the initial position. As a means for determining the position of the culture substrate 8, a vibration unit 10, a weight 2 on the culture substrate 8 loaded on the vibration unit 10 in the vertical direction, and a first holding unit 1 that positions the culture substrate 8 and the weight 2 to maintain the position relative to the vibrator 16 are provided. Figure 2A The positioning member 1 in FIG. 1 is an example of the first holding unit 1. With such a configuration, it is possible to reduce the deviation of the positional relationship between the vibrator 16 and the culture substrate 8 on which cells are mounted from the initial setting.

[0038] The configuration of the cell peeling device 100 according to the embodiment will be specifically described. Initially, the configuration of the culture substrate 8 including the container 7 will be described. The cells 3 are cultured by the culture substrate 8, which is configured to include the container 7 and the lid 6 covering the opening of the container 7, and is in a state of being attached to the bottom of the container 7. The lid 6 provides an obstacle so that contaminants do not touch the cells 3, that is, contaminants are reduced. Desirably, the culture substrate 8 is configured so that the lid 6 fits into the container 7. As will be described later, with the lid 6, in the case of automatically performing opening and placing the counterweight 2, contaminants such as friction dust generated due to contact with the counterweight 2 integrated with the positioning member 1 can be reduced.

[0039] The vibration unit 10 in the cell detachment device 100 according to the present embodiment has a shape such that the culture substrate 8 can be mounted on the upper surface of the vibration unit 10. For example, the bottom of the container 7 is flat, and the vibration surface of the vibration unit 10 is also flat. A vibration transmission medium for further effectively transmitting vibration can be provided between the vibration surface and the culture substrate 8. The vibration transmission medium can be a liquid such as water and ethylene glycol, or a gel, or can be a solid such as silicone rubber. An elastic material such as rubber, which is deformable and easily adhered to tightly, can be used as a sound transmission member.

[0040] As described above, both the vibration surface of the vibration unit 10 and the surface of the bottom of the container 7 are not necessarily flat and may be slightly warped, so when a gap occurs, it is difficult to transmit vibration.

[0041] Therefore, in order to make the bottom of the culture substrate 8 contact the vibration surface uniformly, loading is performed with a force suitable for the warping of the substrate by using the counterweight 2. Desirably, the surface of the counterweight 2 in contact with the culture substrate 8 is also flat, so that the counterweight 2 applies uniform pressure to the culture substrate 8 in a balanced manner.

[0042] In this embodiment, the weight 2 as the second holding unit and the positioning member 1 (first holding unit) holding the weight 2 and providing an instruction to allow the position of the container 7 to be changed are provided. The positioning member 1 may be configured not to constrain the axis in the gravity direction.

[0043] exist Figure 1 and Figure 2A The force applied by the positioning member 1 is shown in FIG. Figure 1In the embodiment, the positioning member 1 is fixed to a table 4 that can be moved in the horizontal direction. By intervening the table 4, the placement position of the culture substrate 8 (wherein the cells 3 are cultured) on the vibration unit 10 can be set so that the deviation from the appropriate position is reduced when vibration is applied. Here, the appropriate position is the position where the force is applied to the adhesion interface of the cell 3. The appropriate position can change over time according to the progress of peeling, and can change according to the vibration mode generated by the vibrator 16 or the aging degradation of the vibrator 16 itself. The applied intensity is expressed as the shape of the vibration transmission medium 9 or the shape of the vibration plate 15, so it is extremely important to move the culture substrate 8 to the appropriate position when vibration is applied. Therefore, a position control unit 14 can be provided, which can change the position of the culture substrate 8 by including a table control loop (its console 4 and the position of the electrically controlled console 4). The switching unit 13 can be used for and configured to switch between the operation of applying vibration from the vibration unit 10 and the operation of changing the position of the culture substrate 8 using the first holding unit 1.

[0044] Second embodiment

[0045] FIG. 3A to FIG. 3E An example of a cell detachment apparatus according to a second embodiment of the present disclosure is shown.

[0046] In the structure in which the counterweight 2 (second holding unit) is supported by being fitted into the positioning member 1 (first holding unit), there is a retraction step for the positioning member 1 and an attachment / detachment step for the counterweight 2. In the structure according to the present embodiment, even with the counterweight 2 whose axis in the gravity direction is not constrained, the positioning member 1 and the counterweight 2 float in the air and are combined into one piece. Figure 3A The figure shows a state where the weight 2 is suspended from the positioning member 1 via a suspension member 21 such as a wire (reinforced fiber, metal wire, musical instrument wire, etc.). Figure 3B In the embodiment, the counterweight 2 is fixed to the positioning member 1 by a sliding shaft 22 and is fitted to the positioning member 1, and the counterweight 2 is suspended via a structure such as a ball bearing, a metal bearing, etc. each time it slides. The counterweight 2 can move up and down, and can be prevented from falling by a stop ring 23. The sliding shaft 22 can be fixed to either the positioning member 1 or the counterweight 2. The suspension member 21 can be made of a soft sheet material such as rubber ( Figure 3C ).

[0047] like Figure 3D and Figure 3E As shown, the positioning member 1 and the weight 2 can be retracted in one operation, resulting in easy attachment / detachment of the culture substrate 8. Figure 3D and Figure 3E States of the positioning member 1 before and after it is rotated around the rotating support 18 are respectively shown.

[0048] When the counterweight 2 as the second holding unit is suspended from the positioning member 1 as the first holding unit by a rope, etc., an effect of balanced loading is obtained. Since the load is caused by gravity, the load is stable, and the inconvenience of difficulty in creating a stable pressure balanced state due to the shape of an elastic member such as a clamp spring, fatigue permanent deformation of the elastic member, etc. as described in Japanese Patent Application Laid-Open No. 2015-043751 can be solved.

[0049] Third embodiment

[0050] FIG. 4A to FIG. 4E An example of a cell detachment apparatus according to a third embodiment of the present disclosure is shown.

[0051] Figure 4A is a schematic cross-sectional view of the cell detachment device according to the present embodiment.

[0052] The support portion 5 and the table 4 are mounted on the bottom plate 12. The vibration unit 10 configured to include a vibration plate 15 and a piezoelectric element 16 (vibrator) is mounted on the support portion 5. The culture substrate 8 is placed on the upper surface of the vibration plate 15, and the weight 2 (second holding unit) is arranged in parallel with a good balance on the upper surface of the substrate shown in the drawing so that the culture substrate 8 is difficult to tilt. Figure 4B As shown, the relationship between the weight 2 and the culture substrate 8 is desirably such that the center of the figure of the culture substrate 8 and the center of gravity position of the weight 2 substantially coincide with each other in the gravity direction (normal direction of the vibration plate 15). Figure 4C and Figure 4D An example of a poorly balanced situation and a state in which a balanced pressure is applied and the weight 2 is not parallel to the upper surface of the substrate is shown. The shape of the weight 2 is not limited to a circle and may be another shape. For example, Figure 4E An example is shown in which the weight 2 has a rectangular shape.

[0053] In this embodiment, if Figure 4A As shown, the deviation can be reduced by providing the fitting portion 11, and a plurality of weights can be selectively arranged to maintain balance.

[0054] Fourth embodiment

[0055] Figure 5 An example of a cell detachment apparatus according to a fourth embodiment of the present disclosure is shown.

[0056] Figure 5 1 is a top view of the cell detachment device according to this embodiment. The support part 5 is fixed on the bottom plate 12 .

[0057] The culture substrate 8 is provided at the center of the support portion 5. The counterweight 2 is placed on the culture substrate 8 and is fitted to the positioning member 1. The table 4 is provided on the bottom plate 12, and the positioning member 1 is fixed to the table 4. When the table 4 moves, the positioning member 1 moves in a direction parallel to the vibration plane of the vibration unit 10 shown in the figure, and the culture substrate 8 also moves via the counterweight 2.

[0058] Fifth embodiment

[0059] FIG. 6A to FIG. 6C An example of a cell detachment apparatus according to a fifth embodiment of the present disclosure is shown.

[0060] In this embodiment, a mode in which the positioning member 1 is assembled to the weight 2 including the fitting portion 11 for fitting to the culture substrate 8 is shown.

[0061] like Fig. 6A As shown, the positioning members 1 are all in the shape of cylindrical pins and are evenly arranged at three positions. Figure 6C As shown, the diameter and Figure 6C The inner diameters of the vibration grooves 26 of the cell detachment device shown are configured to fit into each other. Thus, the same advantageous effects as those of the second embodiment are obtained. Figure 6B As shown, the positioning member 1 and the weight 2 can be retracted in the normal direction (in the figure) in one operation, and the attachment / detachment of the culture substrate 8 is facilitated.

[0062] Sixth Embodiment

[0063] 7A to 7D An example of a cell detachment apparatus according to a sixth embodiment of the present disclosure is shown.

[0064] Fig. 7A A state when the weights 2 are stacked in two stages is shown. Figure 7B The structure in which the counterweights are stacked in two or more stages is shown. Figure 7C As shown, the counterweight 2 and the counterweight 2d can have different shapes. When a plurality of counterweights 2 are stacked, the stacked counterweights 2 can be stable at a lower height, in which case the counterweight 2 can be used. Figure 7C .

[0065] Fig.7D The mode applicable to the second embodiment is shown. With this configuration, the counterweight 2a is suspended from the positioning member 1 through the sliding shaft 22, and a stopper ring 23 for preventing falling is respectively provided at the upper end of the sliding shaft 22 to prevent the sliding shaft 22 from falling. At this time, the counterweight 2b and the counterweight 2c can be stacked on the counterweight 2a.

[0066] Seventh embodiment

[0067] FIG. 8A to FIG. 8DAn example of a cell detachment apparatus according to a seventh embodiment of the present disclosure is shown.

[0068] Here, only the differences from the first embodiment of the present disclosure will be described.

[0069] The cell detachment apparatus according to the present embodiment includes the screw 24 and the friction member 25 on the support 5, and includes the stopper 17. The positioning member 1 is assembled to the screw 24 and rotates in conjunction with the rotation of the screw 24. At this time, when the positioning member 1 rotates to the stopper 17, the positioning member 1 stops rotating in conjunction, and the positioning member 1 rises or falls as in the case of a general screw.

[0070] Fig. 8A and Figure 8B It is a side cross-sectional view and a top view of the positioning member 1 in the state of retreat. When retreating, when the screw rotates counterclockwise, the positioning member 1 rises to the position where the cover 6 of the culture substrate 8 is placed. After that, the positioning member 1 leaves the culture substrate 8, moves to the retreat position, and can move upward to the selected position. Figure 8C and Fig.8D The figure shows a state where the weight 2 and the culture substrate 8 are installed so as to be fittable. Figure 8C and Fig.8D The state in which the positioning member 1 reaches the set position, contacts the stopper 17 and descends when the screw rotates in the reverse direction is shown. In order to stably rotate the positioning member 1 when rotating, it is desirable to apply a certain degree of resistance to the rotating side, and the friction member 25 is a member that applies a load to adjust the rotation resistance.

[0071] For example, if the load is light, the positioning member 1 is pushed back to the opposite side due to the impact caused by hitting the stopper 17, and therefore such a friction member 25 may be provided.

[0072] Eighth Embodiment

[0073] Fig. 9 An example of a cell detachment apparatus according to an eighth embodiment of the present disclosure is shown.

[0074] Only the differences between the cell detachment apparatus according to the present embodiment and the seventh embodiment of the present disclosure will be described.

[0075] In the present embodiment, a rotary actuator 28 is provided, which is one of the components constituting the rotation mechanism (screw 24, friction member 25, and rotary actuator 28), and the culture substrate 8 is automatically moved using the first holding unit 1. As shown in the figure, the rotary actuator 28 can rotate in both the forward and reverse directions, and can be controlled by the position control unit 14 shown in the figure.

[0076] Ninth embodiment

[0077] Fig.10 An example of a cell detachment apparatus according to a ninth embodiment of the present disclosure is shown.

[0078] In the present embodiment, the vibration unit 10 generates ultrasonic vibrations as shown in the figure.

[0079] A disk-shaped vibration unit 10 is provided, which includes a piezoelectric element 16 fixed to a vibration plate 15. An electrode (not shown) for giving an alternating signal is provided on the piezoelectric element 16, and the support portion 5 supports the vibration unit 10. The electrodes (not shown) are provided on the piezoelectric element 16 in such a manner that the front and back sides have opposite polarities so as to cause stretching vibrations. A return electrode is also provided on the front side so as to be electrically connected to the back electrode on the front side. By giving an alternating signal to the piezoelectric material, ultrasonic vibrations can be excited and applied. The piezoelectric element 16 is not necessarily Fig.10 The ring resonator shown may be formed of various vibrators having various shapes, such as a Langevin type, a surface acoustic wave type, and a stacked type, etc. When ultrasonic vibration is used, the container can be easily moved as shown in the figure.

[0080] Tenth embodiment

[0081] FIG. 11A to FIG. 11D An example of a cell detachment apparatus according to a tenth embodiment of the present disclosure is shown.

[0082] In the cell detachment device according to the present embodiment, the counterweight 2 has a contact portion having a uniform flat surface as shown in the figure, and as shown in FIG. Fig.11A As shown, the weight 2 has a shape that allows the weight 2 to apply a load when the center of gravity of the weight 2 is substantially consistent with the center of the protruding upper surface of the culture substrate 8. In order to further achieve uniform contact without gaps, a favorable effect can be obtained by inserting a soft elastic material such as rubber on the flat surface. FIG. 11B to FIG. 11D An example of a structure in which the center of the protruding upper surface of the culture substrate 8 and the center of gravity of the weight 2 do not coincide with each other is shown.

[0083] Eleventh Embodiment

[0084] Fig.12 An example of a cell detachment apparatus according to an eleventh embodiment of the present disclosure is shown.

[0085] Instructions and references Figure 1The differences in the configuration of the cell detachment device according to the embodiment of the present disclosure are described. In the present embodiment, the acoustic transmission medium 9 as a liquid is held by the holding portion 30 for the acoustic transmission medium 9, the culture substrate 8 is in contact with the acoustic transmission medium 9, and the culture substrate 8 is not in contact with the vibration unit 10. The first holding unit 1 holds the culture substrate 8, and the position where the culture substrate 8 is held can be changed by using, for example, a pin of a variable length as the first holding unit 1. Fig.12 As shown, the position of the culture substrate 8 can be constructed to be further easily held by the third holding unit 29. When the third holding unit 29 is made of, for example, a mesh material, and the culture substrate 8 is placed on the mesh material and installed in the sound transmission medium 9 as a liquid, it is easy to hold the position of the culture substrate 8 in a state where the sound transmission medium 9 is in contact with the culture substrate 8.

[0086] With the cell detachment apparatus according to the embodiment of the present disclosure, since appropriate vibration is applied, not only the position of the culture container is maintained, but also the position is allowed to be changed, so the culture container is arranged in an appropriate position and maintained in that position. As a result, it is less likely that the cells are difficult to separate, and the survival rate of the cells is difficult to decrease.

[0087] While the present disclosure has been described with reference to exemplary embodiments, it is to be understood that the present disclosure is 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 and equivalent structures and functions.

Claims

1. A cell detachment device, which separates cells attached to a culture surface of a culture substrate from the culture surface by applying vibration to the culture surface of the culture substrate, the cell detachment device comprising: a vibration unit including a vibrator for generating the vibration; and A first holding unit holds the culture substrate in a manner that allows a position of the culture substrate relative to the vibrator in a horizontal direction to be changed. 2 . The cell detachment apparatus according to claim 1 , further comprising a second holding unit that holds the position of the culture substrate in a vertical direction.

3. The cell detachment device according to claim 2, wherein: The second holding unit is a counterweight.

4. The cell detachment device according to claim 3, wherein: The counterweight is configured to include a plurality of counterweights.

5. The cell detachment device according to claim 3, wherein: The weight is suspended from the first holding unit.

6. The cell detachment device according to claim 2, wherein: The second holding unit includes a pressure applying unit configured to apply pressure in such a manner that a distance between the culture substrate and the vibrator is reduced.

7. The cell detachment device according to claim 1, wherein: The first holding unit includes a fitting portion for being fitted into the culture substrate. 8 . The cell detachment apparatus according to claim 1 , further comprising a rotation mechanism capable of rotating the first holding unit around an axis that is perpendicular to a vibration surface of the vibrator.

9. The cell detachment device according to claim 8, wherein: The rotation mechanism includes a vibrating actuator that rotates the threaded member. 10 . The cell detachment apparatus according to claim 1 , further comprising a position control unit configured to control a position of the culture substrate relative to the vibrator in a horizontal direction.

11. The cell detachment device according to claim 10, further comprising a rotation mechanism capable of rotating the first holding unit around an axis that is perpendicular to the vibration surface of the vibrator, wherein the position control unit controls the rotation of the first holding unit using the rotation mechanism.

12. The cell detachment device according to claim 1, wherein: The first holding unit is configured to be displaceable in a vertical direction.

13. The cell detachment device according to claim 1, wherein: The culture substrate includes a container and a cover, wherein the container has an opening and a culture surface for the cells, and the cover covers the opening.

14. The cell detachment device according to claim 13, wherein: The first holding unit holds the cover.

15. The cell detachment device according to claim 13, wherein: The first holding unit holds the container. 16 . The cell detachment apparatus according to claim 1 , further comprising an acoustic transmission medium between the vibration unit and the culture substrate.

17. The cell detachment device according to claim 16, wherein: The acoustic transmission medium is a liquid, and, The first holding unit is configured so that the culture substrate is in contact with the acoustic transmission medium and the culture substrate is not in contact with the vibration unit.

18. The cell detachment device according to claim 1, wherein: The vibrator generates vibration in the ultrasonic band.

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