The present invention relates to a multi-layer culture vessel observation system, a cart device, and a multi-layer culture vessel observation device for observing objects to be observed in a multi-layer culture vessel including a plurality of trays.
Multi-layer culture vessel observation devices for observing objects to be observed (culture) in a multi-layer culture vessel including a plurality of trays are known. As such a multi-layer culture vessel observation device, a culture vessel observation device in which an optical observation means facing obliquely upward and a lighting means facing obliquely downward are located facing each other with a multi-layer culture vessel therebetween to arrange the optical observation means, the multi-layer culture vessel, and the lighting means on the same optical axis in order to observe the state of cultured cells in each tray is known (for example, see Patent Literature (PTL) 1).
PTL 1: Japanese Patent No. 4049263
Conventionally, in the case of observing objects to be observed in a multi-layer culture vessel by a culture vessel observation device, an operator needs to carry a plurality of multi-layer culture vessels to the vicinity of the culture vessel observation device using a cart, unload a multi-layer culture vessel containing a culture solution from the cart, and then place the multi-layer culture vessel on a pedestal which is an observation position of the culture vessel observation device, to observe objects to be observed in the multi-layer culture vessel. Particularly in the case of observing objects to be observed in each of a plurality of multi-layer culture vessels, the operator needs to load and unload the multi-layer culture vessels containing culture solutions one by one. This increases the labor of the operator. In addition, since the operator manually handles the multi-layer culture vessel, the operator may give an unnecessary impact to the culture medium in the multi-layer culture vessel, or unnecessarily touch the multi-layer culture vessel and consequently damage the multi-layer culture vessel and cause contamination.
The present invention provides a multi-layer culture vessel observation system, a cart device, and a multi-layer culture vessel observation device that enable an operator to easily observe objects to be observed in a multi-layer culture vessel.
A culture vessel observation system according to the present invention is a multi-layer culture vessel observation system including: a cart device capable of carrying a multi-layer culture vessel that includes a plurality of trays and moving; and an observation device capable of observing objects to be observed in each tray in the multi-layer culture vessel, wherein the cart device includes a frame body including a sideways exposure part that exposes two side faces of the multi-layer culture vessel from an upper end to a lower end, wherein the observation device includes: a storage that stores the cart device in a state of carrying the multi-layer culture vessel; and an imaging device that includes an optical system and outputs an image formed by the optical system, and wherein, when the cart device carrying the multi-layer culture vessel is stored in the storage, the sideways exposure part is located on an optical axis of the imaging device.
The culture vessel observation system may further include an operation device that holds and handles the multi-layer culture vessel, wherein the cart device includes: a cart having wheels; and a fixing member that is removably mounted on the cart, and fixes the multi-layer culture vessel to the cart, and wherein the operation device holds and handles the multi-layer culture vessel together with the fixing member.
The culture vessel observation system may further include a lighting device that faces the imaging device, and irradiates the imaging device with light, wherein, when the cart device carrying the multi-layer culture vessel is stored in the storage, the imaging device, the multi-layer culture vessel, and the lighting device are located on the same optical axis, the multi-layer culture vessel being interposed between the imaging device and the lighting device.
The culture vessel observation system may further include a drive portion that drives the imaging device and the lighting device in a first direction and a second direction, wherein the cart has a mounting space in which a plurality of multi-layer culture vessels is mountable side by side in the first direction.
In the multi-layer culture vessel observation system, the imaging device and the lighting device may be arranged so that the optical axis of the imaging device and the lighting device intersects a bottom of the tray in the multi-layer culture vessel at an angle in a range of 40° to 50°.
A cart device according to the present invention is a cart device storable in an observation device capable of observing objects to be observed in each of trays included in a multi-layer culture vessel, including a frame body that fixes the multi-layer culture vessel, wherein the frame body includes a sideways exposure part that exposes two side faces of the multi-layer culture vessel from an upper end to a lower end.
In the cart device, the frame body may comprise a plurality of frame bodies.
A multi-layer culture vessel observation device according to the present invention is a multi-layer culture vessel observation device including: a storage that stores the cart device described above in a state of carrying the multi-layer culture vessel; and an imaging device that includes an optical system and outputs an image formed by the optical system, wherein, when the cart device carrying the multi-layer culture vessel is stored in the storage, the sideways exposure part is located on an optical axis of the imaging device.
According to the present invention, it is possible to provide a multi-layer culture vessel observation system, a cart device, and a multi-layer culture vessel observation device that enable an operator to easily observe objects to be observed in a multi-layer culture vessel.
A multi-layer culture vessel observation system 1 according to an embodiment will be described below. The multi-layer culture vessel observation system 1 according to this embodiment is a system for observing cultured cells in a multi-layer culture vessel 30 used in cell culture and the like. The multi-layer culture vessel 30 according to this embodiment will be described first.
To observe cultured cells in such a multi-layer culture vessel 30, the multi-layer culture vessel observation system 1 according to this embodiment includes a multi-layer culture vessel observation device 10 and a cart device 20, as illustrated in
The fixing member 23 can simultaneously fix a plurality of multi-layer culture vessels 30 in a state in which the plurality of multi-layer culture vessels 30 are arranged side by side, as illustrated in
As illustrated in (A) in
The lateral frame members 251 can fix the multi-layer culture vessel 30 by being attached to the frame member 25, as illustrated in
The multi-layer culture vessel observation device 10 according to this embodiment will be described below.
The imaging device 11 is a camera that includes a lens and focuses on the bottom of each tray 31 in the multi-layer culture vessel 30 and images cultured cells adhering to the bottom of the tray 31. The imaging device 11 is not limited as long as it is a camera, but preferably includes a zoom lens and is capable of capturing an image of each tray 31 with different magnification. In this embodiment, the imaging device 11 engages with the first frame 111 extending in the X-axis direction, and can be moved in the X-axis direction along the first frame 111 by the drive portion 13. The first frame 111 engages with the second frame 112 extending in the Z-axis direction, and can be moved in the Z-axis direction along the second frame 112 by the drive portion 13, as a result of which the imaging device 11 can be moved in the Z-axis direction, too. Thus, the imaging device 11 can be moved in a two-dimensional direction (XZ-axis direction) along the first frame 111 and the second frame 112 by the drive portion 13. The drive portion 13 includes an electric motor and/or an air cylinder, and can drive the frames 111 to 114 by the electric motor and/or air cylinder.
The lighting device 12 is a lighting device that irradiates the imaging device 11 with light. The lighting device 12 is not limited, and may be, for example, a lighting device having LEDs as a light source. In this embodiment, the lighting device 12 engages with the third frame 121, and can be moved in the X-axis direction along the third frame 121 by the drive portion 13. The third frame 121 engages with the fourth frame 122, and can be moved in the Z-axis direction along the fourth frame 122 by the drive portion 13, as a result of which the lighting device 12 can be moved in the Z-axis direction, too. Thus, the lighting device 12 can be moved in the two-dimensional direction (XZ-axis direction) along the third frame 121 and the fourth frame 122 by the drive portion 13, as with the imaging device 11.
In this embodiment, when the cart device 20 carrying the multi-layer culture vessel 30 is stored in the storage 14, the imaging device 11 and the lighting device 12 are arranged facing each other with the multi-layer culture vessel 30 therebetween, as illustrated in
The imaging device 11 and the lighting device 12 are preferably arranged on the same optical axis L that passes the multi-layer culture vessel 30 obliquely, as illustrated in
In this embodiment, in the case where the cart device 20 carrying the multi-layer culture vessel 30 is stored in the storage 14, the cart device 20 is stored in the storage 14 with the lateral frame members 251 being removed from the frame member 25 as illustrated in
The drive portion 13 moves the imaging device 11 and the lighting device 12 in the two-dimensional direction (XZ-axis direction). In particular, in this embodiment, the drive portion 13 moves the imaging device 11 and the lighting device 12 in the same direction by the same distance so that the imaging device 11 and the lighting device 12 will be located on the same optical axis L and the relative positions of the imaging device 11 and the lighting device 12 will be unchanged. For example, in this embodiment, the operator can operate the touch panel portion 15 to designate the position of the tray 31 to be observed, as described later. In the case where the operator operates the touch panel portion 15 to issue an instruction for movement of 5 mm in the X-axis positive direction, for example, the drive portion 13 drives the imaging device 11 to move 5 mm in the X-axis positive direction along the first frame 111, and drives the lighting device 12 to move 5 mm in the X-axis positive direction along the third frame 121. Moreover, the drive portion 13 can move the imaging device 11 and the lighting device 12 in the vertical direction (Z direction) to observe a tray 31 in a different layer (stage), and move the imaging device 11 and the lighting device 12 in the right-left direction (X direction) to observe a different multi-layer culture vessel 30.
The storage 14 is a space for storing the cart device 20 carrying the multi-layer culture vessel 30. The storage 14 includes a fixture for fixing the cart device 20 in a predetermined observation position. Thus, the cart device 20 can be fixed in the observation position in the storage 14, and the imaging device 11 can image the cultured cells in each tray 31 in the multi-layer culture vessel 30. A door 141 is installed at the entrance of the storage 14.
The touch panel portion 15 functions as an input portion for the operator to input instructions, and also functions as a display portion for displaying images captured by the imaging device 11. In this embodiment, the display region of the display of the touch panel portion 15 is divided between a display region for input and a display region for captured image display, and a captured image is displayed in the display region for captured image display and buttons (icons) for the operator to input instructions are displayed in the display region for input. The operator can designate the position of imaging by the imaging device 11 or the like, by pressing a corresponding button (icon) displayed in the display region for input.
The control portion 16 includes read only memory (ROM) that stores a program, a central processing unit (CPU) that executes the program stored in the ROM, and random access memory (RAM) that functions as an accessible storage device. Based on the program stored beforehand, the control portion 16 displays an image captured by the imaging device 11 on the touch panel portion 15 and outputs a drive instruction to the drive portion 13 based on an instruction input to the touch panel portion 15 by the operator. The fan 17 is provided above the control portion 16. The fan 17 is installed to perform suction for the control portion 16, as a result of which the control portion 16 can be cooled. Since the multi-layer culture vessel observation device 10 according to this embodiment is often used at relatively high temperature (e.g. 37° C.) suitable for culture, the provision of the fan 17 can reduce the possibility that the control portion 16 fails due to heat.
As described above, in the multi-layer culture vessel observation system according to Embodiment 1, the cultured cells in each tray 31 in each multi-layer culture vessel 30 can be observed in a state in which the cart device 20 carries the multi-layer culture vessel 30. Since there is no need to place the multi-layer culture vessels 30 in the dedicated observation position (pedestal) one by one as in the conventional techniques, the labor of the operator can be reduced. Moreover, the operator can be prevented from giving an unnecessary impact to the culture medium in the multi-layer culture vessel 30, and unnecessarily touching the multi-layer culture vessel 30. Furthermore, in the multi-layer culture vessel observation system 1 according to this embodiment, a plurality of multi-layer culture vessels 30 can be mounted on one cart device 20 simultaneously, so that the cultured cells in the trays 31 of the plurality of multi-layer culture vessels 30 can be observed at one time.
A multi-layer culture vessel observation system 1a according to Embodiment 2 will be described below. The multi-layer culture vessel observation system 1a according to Embodiment 2 includes a multi-layer culture vessel operation device 40 for operating (handling) the multi-layer culture vessel 30, in addition to the structure of the multi-layer culture vessel observation system 1 according to Embodiment 1.
In detail, the system according to Embodiment 2 is configured to perform a series of operations of introducing a culture solution seeded with cells into the multi-layer culture vessel 30 using the multi-layer culture vessel operation device 40, culturing the cells in the multi-layer culture vessel 30 for a certain period of time, and then observing the cultured cells using the multi-layer culture vessel observation device 10, in a state in which the cart device 20 carries the multi-layer culture vessel 30. The multi-layer culture vessel operation device 40 will be described below.
The multi-layer culture vessel operation device 40 is a device (manipulator) for operating the multi-layer culture vessel 30.
As illustrated in
The multi-layer culture vessel operation device 40 includes the pair of arms 48 that function as a support member for supporting the multi-layer culture vessel 30. The pair of arms 48 are insertable through two insertion holes 27 formed in the fixing member 23, as illustrated in
The drive control portion 45 then causes the rotation drive portion 42 to perform a rotation operation of rotating the rotation portion 41 around two axes, i.e. rotation axes X1 and X2, as indicated by reference signs R and P in
The rotation drive portion 42 can rotate the rotation portion 41 (multi-layer culture vessel 30) in the roll direction R around the rotation axis X1 and in the pitch direction P around the rotation axis X2, as illustrated in (C) and (D) in
The rotation drive portion 42 can also perform a swinging operation of reciprocatingly rotating the rotation portion 41 (multi-layer culture vessel 30) around the rotation axis X1 or the rotation axis X2. For example, the rotation drive portion 42 can perform a swinging operation around the rotation axis X1, by reciprocatingly rotating the rotation portion 41 (multi-layer culture vessel 30) in the roll direction R within a range of ±120° around the rotation axis X1. The rotation drive portion 42 can also perform a swinging operation around the rotation axis X2, by reciprocatingly rotating the rotation portion 41 (multi-layer culture vessel 30) in the pitch direction P within a range of ±20° around the rotation axis X2 so as to tilt the upper part of the rotation portion 41 (multi-layer culture vessel 30) forward (X-axis negative direction) and then tilt the lower part of the rotation portion 41 (multi-layer culture vessel 30) forward (X-axis negative direction).
The shaking portion 43 is stored inside the body 49 of the multi-layer culture vessel operation device 40 when not performing the below-described shaking operation. When performing the shaking operation, the shaking portion 43 is protruded to the outside of the body 49 by the shaking drive portion 44 under control of the drive control portion 45, as illustrated in
In this embodiment, the drive control portion 45 can cause the shaking portion 43 to perform the shaking operation following the rotation operation by the rotation portion 41. In this case, after the rotation operation by the rotation portion 41 ends, the drive control portion 45 controls the arm drive portion 47 to drive the pair of arms 48 downward (Z-axis negative direction) so that the multi-layer culture vessel 30 together with the fixing member 23 will be placed on the upper surface 431 of the shaking portion 43. The drive control portion 45 then controls the shaking drive portion 44 to cause the shaking portion 43 to perform the shaking operation of shaking the multi-layer culture vessel 30. In this embodiment, the shaking operation is performed in a state in which the arms 48 remain protruding without being stored in the body 49. In this embodiment, the inner width W3 of the insertion hole 27 is greater than the sum of the outer width W2 of the arm 48 and the shaking width of the shaking portion 43 as illustrated in
The drive control portion 45 can cause the rotation portion 41 to perform the rotation operation following the shaking operation by the shaking portion 43. In this case, after the shaking operation by the shaking portion 43 ends, the drive control portion 45 controls the arm drive portion 47 to drive the pair of arms 48 upward (Z-axis positive direction) so that the multi-layer culture vessel 30 together with the fixing member 23 will be lifted upward. The drive control portion 45 then controls the shaking drive portion 44 to store the shaking portion 43 inside the body 49, and subsequently controls the rotation drive portion 42 to cause the rotation portion 41 to perform the rotation operation.
As mentioned above, in the case of operating the cart device 20 carrying the multi-layer culture vessel 30 by the multi-layer culture vessel operation device 40, it is preferable to attach the lateral frame members 251 to the frame member 25 as illustrated in
The operation portion 46 is a device for the operator to input instructions, and may include, for example, a touch panel. By operating the operation portion 46, the operator can transmit, to the drive control portion 45, an instruction such as starting, halting, or ending the program stored in the drive control portion 45 beforehand, to start, halt, or end the operation of the rotation portion 41 or the shaking portion 43, for example. Moreover, by operating the operation portion 46, the operator can cause the drive control portion 45 to store a new program or partially change the stored program. For example, by operating the operation portion 46, the operator can change the inclination angle of the rotation axis X1 of the rotation portion 41 from 100° to 120° in the culture solution recovery process of recovering the culture solution from the multi-layer culture vessel 30.
Thus, the multi-layer culture vessel operation device 40 according to this embodiment lifts the fixing member 23 fixing the multi-layer culture vessel 30 from the cart device 20 and holds the fixing member 23 fixing the multi-layer culture vessel 30 and performs the rotation operation and the shaking operation of the multi-layer culture vessel 30. In this way, the series of processes, i.e. the introduction of the culture solution seeded with cells into the multi-layer culture vessel 30, and, after the cell culture, the recovery of the culture solution, the introduction of the trypsin solution into the multi-layer culture vessel 30, the cell detachment, and the recovery of the trypsin solution after the cell detachment, can be performed without the operator touching the multi-layer culture vessel 30. With the conventional techniques, after introducing the trypsin solution into the multi-layer culture vessel 30, the operator manually removes the multi-layer culture vessel 30 from the multi-layer culture vessel operation device, places the multi-layer culture vessel 30 on a dedicated shaker, shakes the multi-layer culture vessel 30 by the dedicated shaker, and then manually places the multi-layer culture vessel 30 on the multi-layer culture vessel operation device again to perform the trypsin solution recovery process. This increases the labor of the operator in the cell culture process. In addition, due to the manual operation by the operator, the operation may vary, or the operator may unnecessarily touch the multi-layer culture vessel 30 and consequently damage the multi-layer culture vessel and cause contamination. With the multi-layer culture vessel operation device 40 according to this embodiment, such problems can be solved because the foregoing series of processes can be performed without the operator touching the multi-layer culture vessel 30.
The multi-layer culture vessel observation system 1a according to Embodiment 2 includes the multi-layer culture vessel operation device 40, so that the series of processes, i.e. the introduction of the culture solution into the multi-layer culture vessel 30, the cell culture, the observation of the cultured cells, and the recovery of the cultured cells, can be performed without the operator touching the multi-layer culture vessel 30. That is, the operator can introduce the culture solution seeded with cells into the multi-layer culture vessel 30 using the multi-layer culture vessel operation device 40, and subsequently return the multi-layer culture vessel 30 to the cart device 20 directly from the multi-layer culture vessel operation device 40 and move the multi-layer culture vessel 30 to a culture chamber or the like by the cart device 20. Moreover, in the case of observing the cultured cells, the operator can move the multi-layer culture vessel 30 mounted on the cart device 20 into the storage 14 of the multi-layer culture vessel observation device 10 and, in a state in which the cart device 20 carries the multi-layer culture vessel 30, observe the cultured cells using the multi-layer culture vessel observation device 10. Further, in the case where the operator determines that the cell culture is completed as a result of the observation, the operator can perform the culture solution recovery process, the trypsin solution introduction process, the cell detachment process, and the trypsin solution recovery process by the multi-layer culture vessel operation device 40, while the multi-layer culture vessel 30 is held by the multi-layer culture vessel operation device 40.
As described above, in the multi-layer culture vessel observation system 1a according to Embodiment 2, the multi-layer culture vessel 30 can be operated and observed without the operator touching the multi-layer culture vessel 30. Hence, the series of processes, i.e. the introduction of the culture solution seeded with cells into the multi-layer culture vessel 30, the cell culture, the observation of the cultured cells, and the recovery of the cultured cells, can be performed without the operator touching the multi-layer culture vessel 30. This can reduce the labor of the operator in mass cell culture, and effectively prevent the cultured cells from being adversely affected as a result of the operator giving an unnecessary impact to the culture medium in the multi-layer culture vessel 30 or unnecessarily touching the multi-layer culture vessel 30.
A multi-layer culture vessel observation system 1b according to Embodiment 3 mainly differs from the multi-layer culture vessel observation system 1a according to Embodiment 2 in that a multi-layer culture vessel operation device 40a does not include the shaking portion 43 and the shaking drive portion 44. Hereafter, the same components as in Embodiment 2 are given the same reference signs, and their description is omitted.
The rotation drive portion 42 includes a first electric motor that rotates the rotation portion 41 around the rotation axis X1 and a second electric motor that rotates the rotation portion 41 around the rotation axis X2.
The operation program causes the cell detachment process to be performed by the rotation portion 41 reciprocatingly swinging the multi-layer culture vessel 30 in a first direction (e.g. to the right) and in a second direction (e.g. to the left) around a first rotation axis or a second rotation axis. The operation program defines a stop mode in which the movement of the multi-layer culture vessel 30 is stopped for a designated time when switching from the rotation operation in the first direction to the rotation operation in the second direction and when switching from the rotation operation in the second direction to the rotation operation in the first direction.
With the stop mode, even in the case where the speed of the swinging operation is higher than the speed of the movement of the liquid in the vessel, by stopping the swinging operation for the designated time when switching the direction of the rotation operation, the liquid in the vessel can reliably collide with the side surface (side wall) of the vessel. While it is important to swing the vessel at high speed for an effective cell detachment process, the delay (time lag) of the movement of the liquid which occurs when swinging the vessel at high speed can be resolved in this way.
The operation program causes an operation of recovering cells adhering to the side surface of each tray 31 to be performed before the trypsin solution recovery process. In the case where each tray 31 is a rectangular tray having first to fourth side surfaces, the rotation portion 41 is operated so that the trypsin solution will collide with the first side surface, the second side surface, the third side surface, and the fourth side surface in this order. With such operation, the trypsin solution recovery process can be performed after recovering, in the trypsin solution, the cells adhering to the side surface of each tray 31.
The multi-layer culture vessel operation device 40a according to Embodiment 3 described above has the same advantageous effects as in Embodiment 2.
Moreover, according to Embodiment 3, the cell detachment process is possible without the shaking portion 43. Since the device structure is simple, the manufacturing costs can be reduced.
Furthermore, the stop mode can resolve the delay (time lag) of the movement of the liquid which occurs when swinging the vessel at high speed.
While some preferred embodiments of the present invention have been described above, the technical scope of the present invention is not limited to the foregoing embodiments. Various modifications and improvements can be made to the foregoing embodiments, and such modifications and improvements are also included in the technical scope of the present invention.
For example, although the foregoing embodiments describe an example in which the multi-layer culture vessel observation device 10 includes the touch panel portion 15, the present invention is not limited to such. For example, the multi-layer culture vessel observation device 10 may separately include an input portion for the operator to input instructions and a display portion for displaying images captured by the imaging device 11.
Although the foregoing embodiments describe an example in which the multi-layer culture vessel observation systems 1 to 1b and the multi-layer culture vessel observation device 10 are used in observation of cultured cells, the present invention is not limited to such. The multi-layer culture vessel observation systems 1 to 1b and the multi-layer culture vessel observation device 10 may be used in observation of cultured microorganisms.
The multi-layer culture vessel observation device 10 may have any of the following structures, in addition to the foregoing embodiments.
In the case where the drive portion 13 is formed by an air cylinder, the multi-layer culture vessel observation device 10 may include a pressure sensor for monitoring the pressure of the air cylinder. By monitoring the air pressure of the air cylinder by the pressure sensor, a failure of the air cylinder can be detected.
The control portion 16 may be configured to count the number of times the drive portion 13 is operated. The control portion 16 may be configured to predict when to replace an electric motor or an air cylinder included in the drive portion 13, based on the number of times the drive portion 13 is operated.
The control portion 16 may be configured to measure the total operation time of the drive portion 13. The control portion 16 may be configured to predict when to replace an AC/DC power source, a battery, the fan 17, or the like, based on the total operation time of the drive portion 13.
The multi-layer culture vessel operation devices 40 and 40a may each have any of the following structures, in addition to Embodiments 2 and 3.
In the case where the rotation drive portion 42 and the arm drive portion 47 are formed by an air cylinder, the multi-layer culture vessel operation devices 40 and 40a may each include a pressure sensor for monitoring the pressure of the air cylinder. By monitoring the air pressure of the air cylinder by the pressure sensor, a failure of the air cylinder can be detected.
The multi-layer culture vessel operation devices 40 and 40a may each include an area sensor. By constantly monitoring, by the area sensor, whether anyone comes near the multi-layer culture vessel operation device and in particular the rotation portion 41, safety can be improved.
The drive control portion 45 may be configured to count the number of times the rotation portion 41, the shaking portion 43, or the arms 48 are operated. The drive control portion 45 may be configured to predict when to replace an electric motor or an air cylinder included in the rotation drive portion 42, the shaking drive portion 44, or the arm drive portion 47, based on the number of times the rotation portion 41, the shaking portion 43, or the arms 48 are operated.
The drive control portion 45 may be configured to measure the total operation time of the rotation portion 41, the shaking portion 43, or the arms 48. The drive control portion 45 may be configured to predict when to replace an AC/DC power source, a battery, a fan, or the like, based on the total operation time of the rotation portion 41, the shaking portion 43, or the arms 48.
Although the foregoing embodiments describe an example in which the cart device 20 includes a pair of lateral frame members 251, the present invention is not limited to such. For example, the cart device 20 may include a plurality of pairs of lateral frame members 251.
Number | Date | Country | Kind |
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2018-103807 | May 2018 | JP | national |
Filing Document | Filing Date | Country | Kind |
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PCT/JP2019/000621 | 1/11/2019 | WO | 00 |