JP2012152124A - Culture observation apparatus - Google Patents

Abstract

PROBLEM TO BE SOLVED: To prevent the movement of cells caused by the rotation when a culture vessel is conveyed.SOLUTION: A culture observation apparatus includes: a storage where two or more culture vessels for culturing the cells are stored; an observation device for observing the cells cultured in the culture vessel; and a conveyor for holding and conveying the culture vessel from one of the storage and the observation apparatus to the other by a conveying operation combining a linear motion to move the culture vessel in the horizontal direction and a rotational motion to rotate with an axis vertical to the horizontal direction of the culture vessel as the rotation center, the conveyor including a first rotation mechanism that rotates the culture vessel in a direction opposite to the rotating direction of the rotational motion to maintain the culture vessel in the posture immediately after being held by the conveyor.

Description

  The present invention relates to a culture observation apparatus for culturing cells.

  A culture observation apparatus is known as an apparatus for automatically observing cultured cells. This culture observation apparatus is a storage room (hereinafter referred to as a stocker) for storing a culture container in which cells are cultured in a constant temperature room provided therein, an observation apparatus such as a microscope for observing the cells in the culture container, A transport device for transporting the culture container between the stocker and the observation device is disposed. This culture observation apparatus has a layout in which the stocker and the observation apparatus are opposed to each other and a conveyance apparatus is disposed between these apparatuses in consideration of so-called culture container conveyance efficiency (see Patent Document 1). . With such a layout, the transport device performs a transport operation that combines a linear motion and a rotational motion in the three directions of the x direction, the y direction, and the z direction.

Japanese Patent No. 4334432

  By the way, the above-described cells are uniformly seeded in the culture solution in the culture vessel. However, when a rotation operation is performed by the transport device during transport of the culture container, cells floating in the culture solution in the culture container, such as cells immediately after being seeded and cells not adhered to the bottom surface of the culture container, As a result, the cells are collected at predetermined positions in the culture container, and the distribution of the cells is uneven. Such uneven distribution of cells can cause the cells in the culture vessel to not grow uniformly, and can cause the cells to be observed where many cells cannot be observed or where many cells can be observed. There is a problem of affecting.

  The present invention prevents the movement of the cells due to the rotation operation during the conveyance of the culture container, thereby allowing the cells in the culture container to grow uniformly and not affecting the observation of the cells. An object of the present invention is to provide a culture observation apparatus.

  The culture observation apparatus of the present invention is a storage in which a plurality of culture containers in which cells are cultured is stored, an observation apparatus that observes the cells cultured in the culture container, and the culture container that moves in the horizontal direction. The culture container is held in the storage container and the observation apparatus in a state where the culture container is held by a transport operation that combines a linear operation and a rotation operation that rotates about an axis perpendicular to the horizontal direction of the culture vessel. A conveying device that conveys from one side to the other, and the conveying device is rotated in a direction opposite to the rotational direction of the rotating operation, and the posture of the culture vessel is held by the conveying device. A first rotation mechanism that maintains the immediately following posture is provided.

  In addition, the rotation amount in the first rotation mechanism is the same as the rotation amount in the rotation operation in the transport device, and the rotation of the culture vessel in the first rotation mechanism is in accordance with the rotation operation of the transport device. Is executed.

  In addition, the transport device includes a second rotation mechanism that performs the rotation operation, and the first rotation mechanism and the second rotation mechanism are provided independently of each other.

  In addition, the transport device further includes a holding unit that holds the culture vessel and a moving mechanism that performs the linear operation, and the first rotating mechanism includes a mechanism that rotates the holding unit, The second rotating mechanism includes a mechanism that simultaneously rotates the moving mechanism and the second rotating mechanism.

  According to the present invention, by preventing the movement of the cells due to the rotation operation during the transportation of the culture container, the cells in the culture container can be grown uniformly and the observation of the cells can be prevented.

It is a front view which shows the outline of a culture observation apparatus. It is a front view which shows the outline of the culture observation apparatus which opened the outer door. It is the schematic which shows the structure inside a temperature-controlled room. (A) is a front view which shows the structure of the principal part of a conveyance unit, (b) is a side view which shows the structure of the principal part of a conveyance unit. (A) Container transport device before holding the culture vessel, (b) Container transport device holding the culture vessel by the holding mechanism, (c) Top view showing the container transport device immediately after the held culture vessel is unloaded from the stocker It is. (A) Container transport apparatus immediately after rotating while holding the culture container, (b) Container transport apparatus immediately after placing the culture container on the container placement surface of the observation apparatus, (c) Immediately after transporting the culture container It is a top view which shows this container conveyance apparatus.

  Hereinafter, the structure of the culture observation apparatus of this embodiment is shown in detail. In addition, the culture observation apparatus shown below is an example, and is not limited to the configuration of the culture observation apparatus shown in the present embodiment. As shown in FIGS. 1 to 3, the culture observation apparatus 10 includes a first housing 11 that cultures a sample such as a microorganism or a cell, and a second housing 12 that houses a control device 13. In the assembled state of the culture observation apparatus 10, the first housing 11 is disposed on the upper portion of the second housing 12.

  The first housing 11 includes a temperature-controlled room 15 whose interior is covered with a heat insulating material. The temperature-controlled room 15 communicates with the outside through a front opening 16 formed on the front surface of the first housing 11. The front opening 16 of the first housing 11 is closed by an inner door 17 and two outer doors 18a and 18b. Packing etc. are provided in the peripheral part of the back side of this inner door 17 and outer doors 18a and 18b, and the inside of temperature-controlled room 15 is kept airtight when each door is closed. That is, when only the inner door 17 is closed, or when not only the inner door 17 but also the two outer doors 18a and 18b are respectively closed, the outside of the culture observation apparatus 10 is moved into the temperature-controlled room 15 from the outside. Inflow of heat and outflow of heat from the inside of the temperature-controlled room 15 to the outside of the culture observation apparatus 10 are prevented. Note that the inside of the temperature-controlled room 15 is managed so as to have predetermined environmental conditions (temperature, humidity, carbon dioxide concentration, etc.) by a temperature adjustment device, a spray device, etc. (not shown).

  Of the outer doors 18a and 18b described above, the outer door 18b is provided with a loading door 22. The carry-in door 22 is opened when the carrier 25 containing the culture vessel 31 is carried into the carrier installation table 26 or when the carrier 25 installed on the carrier installation table 26 is carried out. When the loading door 22 is opened, the small door 24 provided on the inner door 17 is exposed through the opening 23. The inner door 17 and the small door 24 are made of glass or transparent synthetic resin, and even when the outer doors 18a and 18b are opened, the internal environmental conditions do not change abruptly. . By opening the small door 24 provided in the inner door 17, the carrier 25 in which the culture vessel 31 is stored can be carried into the carrier installation base 26, or the carrier 25 installed on the carrier installation base 26 can be carried out. It becomes possible. In addition, the carrier 25 can accommodate three culture containers 31, for example, up and down at a predetermined interval.

  Inside the temperature-controlled room 15, a carrier installation table 26, a stocker 27, an observation device 28, a container transport device 29, and the like are arranged. In addition, although illustration is abbreviate | omitted, the inside of this temperature-controlled room 15 is provided with the culture medium exchange mechanism which performs culture medium exchange, the seeding mechanism which seeds | inoculates a cell, etc.

  As described above, the carrier installation table 26 has the carrier 25 placed thereon. Although illustration is omitted, the carrier installation base 26 is provided with guide rails on the side surfaces. This guide rail restricts the moving direction of the carrier 25 that is carried in or out by entering a guide groove provided at an interval where the guide rail enters the lower surface of the carrier 25. The extending direction of the guide groove is orthogonal to the direction in which the culture vessel 31 is carried into the carrier 25 or the direction in which the culture vessel 31 is carried out from the carrier 25.

  The stocker 27 is disposed on the left side of the temperature-controlled room 15 when viewed from the front of the first housing 11. The stocker 27 has a plurality of shelves in the vertical direction, and the culture vessel 31 is stored in each shelf. In the stocker 27, a position for storing each culture vessel 31 (hereinafter referred to as a storage position) is set in advance. Each storage position is associated with an identification number for distinguishing it from other storage positions, and by this identification number, an observation schedule of cells to be cultured, image data obtained at the time of observation, and the like are managed collectively. . In the culture vessel 31 described above, a sample to be cultured such as a cell is held together with the culture solution 33.

  The main body of the observation device 28 is installed inside the second housing 12, and the upper portion of the observation device 28 is arranged so as to enter the inside from the lower side of the first housing 11. The observation device 28 is disposed on the right side of the temperature-controlled room 15 when viewed from the front of the first housing 11. Further, the observation device 28 is disposed by being fitted into the opening on the bottom surface of the first housing 11. Although the configuration of the observation device 28 is omitted, examples of the observation device 28 include a microscope capable of performing observation methods such as phase difference observation, fluorescence observation, and differential interference observation.

  The observation device 28 observes the culture container 31 stored in the carrier 25 immediately after being installed on the carrier installation table 26 or the cells cultured in the culture container 31 in which the fixing time has elapsed since being stored in the stocker 27. During this observation, the entire image data of the culture vessel 31 and the image data of the cells to be cultured are acquired. Each image data acquired by the observation device 28 is output to the control device 13. In addition to controlling the observation device 28, the container transport device 29, and the like, the control device 13 provides information such as the type of cells to be cultured, the observation schedule, etc. for each identification number associated with each storage position of the stocker 27, The image data acquired by the observation device 28 is stored in association with each other.

  As shown in FIG. 2 to FIG. 4, the container transport device 29 is disposed in the approximate center of the temperature-controlled room 15 when viewed from the front of the first housing 11. The container transport device 29 transports the culture container 31 stored in the carrier 25 toward the stocker 27 and the observation device 28 (or vice versa), or the culture container 31 stored in the stocker 27 as the carrier 25 and the observation device. Transport toward device 28 (or vice versa).

  The container transport device 29 is a drive that independently executes a linear operation in the three-axis directions of the X axis, the Y axis, and the Z axis, and a rotation operation about the axis Z1 and a rotation operation about the axis Z2. A device provided with a mechanism.

  The lower base plate 41 is attached to the guide shafts 42 and 43 and the drive shaft 44. When the motor 45 is driven, the drive shaft 44 rotates. In accordance with the rotation of the drive shaft 44, the lower base plate 41 moves along the guide shafts 42 and 43 (in the Y-axis direction).

  A motor 46 is provided in the approximate center of the lower base plate 41. A drive shaft 47 of the motor 46 is attached to the upper base plate 48. When the motor 46 is driven, the drive shaft 47 rotates and the upper base plate 48 rotates about the axis Z1.

  Guide shafts 49 and 50 and a drive shaft 51 are provided on the upper surface of the upper base plate 48. A carriage 52 is attached to the guide shafts 49 and 50 and the drive shaft 51. When the motor 53 is driven, the drive shaft 51 rotates. In accordance with the rotation of the drive shaft 51, the transport base 52 moves along the guide shafts 49 and 50 (in the Z-axis direction).

  As for the conveyance stand 52, the conveyance stand 55 is attached to the lower surface side. As for the conveyance stand 55, the guide rail 52a provided in the lower surface of the conveyance stand 52 is penetrated by guide grooves, such as a rail groove provided in the one end part. When a motor (not shown) is driven, the drive shaft 54 is rotated, and the transport base 55 is moved along the guide rail 52a (in the X-axis direction).

  A motor 56 is provided at the other end of the transport table 55. A drive shaft 57 of the motor 56 is attached to a holding mechanism 58. When the motor 56 is driven, the drive shaft 57 rotates and the holding mechanism 58 rotates about the axis Z2.

  The holding mechanism 58 includes two grip pieces 59 and 60 that are arranged at a predetermined interval. These grip pieces 59 and 60 are moved between the position of the solid line in FIG. 4B and the position of the two-dot chain line by a drive mechanism using air pressure or hydraulic pressure, or a drive mechanism using a motor and gear, for example. Move each one. These holding pieces 59, 60 move to the position indicated by the solid line in FIG. 4B when holding the culture vessel 31, and are held at that position. At this time, the culture vessel 31 is sandwiched between the gripping pieces 59 and 60 in the short direction. That is, the culture vessel 31 is held by the gripping pieces 59 and 60. In addition, when the culture container 31 is held by the gripping pieces 59 and 60, if the gripping pieces 59 and 60 move in the direction away from each other to the position of the two-dot chain line in the figure, the culture container 31 by the gripping pieces 59 and 60 is used. Is released. That is, the holding of the culture vessel 31 is released.

  The position (coordinates) and the rotation angle of each part of the container transport device 29 are monitored by the control device 13 via an encoder or the like. The control device 13 stores in advance data on the positions of the carrier 25, the stocker 27, and the observation device 28. From these data and data obtained by monitoring of the container transport device 29, each part of the container transport device 29 is controlled. Drive control.

  Next, operation | movement of the container conveying apparatus 29 of this embodiment is demonstrated. Hereinafter, the case where the culture container 31 stored in the stocker 27 is transported toward the observation device 28 will be described.

  First, the control device 13 confirms the position in the Y direction of the container transport device 29 and determines whether or not it is in the same position as the position in the Y direction of the culture vessel 31 for observing cells. When the position in the Y direction of the container transport device 29 is different from the position in the Y direction of the culture vessel 31 for observing cells, the control device 13 drives the motor 45 and rotates the drive shaft 44. The rotation of the drive shaft 44 moves the lower base plate 41 in the direction or direction. And the control apparatus 13 stops the drive of the motor 45, when the container conveying apparatus 29 becomes the same position in the Y direction as the culture container 31 which observes a cell. Thereby, the rotation of the drive shaft 44 is stopped and the movement of the lower base plate 41 is stopped. Note that this operation is not performed when the position of the container transport device 29 in the Y direction is the same as the position of the culture container 31 stored in the stocker 27 in the Y direction.

  Next, the control device 13 determines the rotational position of the transport table 52. For example, when the transport table 52 of the container transport device 29 is at the rotational position where the state shown in FIG. 4A is obtained, the motor 46 is driven and the drive shaft 47 is rotated. The upper base plate 48 rotates in accordance with the rotation of the drive shaft 47. Then, when the upper base plate 48 rotates 180 °, the control device 13 stops driving the motor 46. As a result, the rotation of the drive shaft 47 stops. As a result, the upper base plate 48 is rotated 180 ° (see FIG. 5A). On the other hand, when the rotation position of the transport table 52 is in the state shown in FIG.

  The control device 13 determines the position of the holding mechanism 58 in the Z direction. For example, when the holding mechanism 58 is not in a position where the culture container 31 of the stocker 27 can be gripped, the motor 53 is driven and the drive shaft 51 is rotated. Due to the rotation of the drive shaft 51, the transport table 52 is raised or lowered. The control device 13 stops the driving of the motor 53 when the holding mechanism 58 reaches a position where the culture container 31 of the stocker 27 can be gripped. Thereby, the movement of the conveyance stand 52 stops. In addition, when the holding mechanism 58 is in a position where the culture container 31 of the stocker 27 can be gripped, the above-described operation is not executed.

  Next, the control device 13 drives a motor (not shown) to rotate the drive shaft 54. Due to the rotation of the drive shaft 54, the transport table 55 moves in the X1 direction. When the transport table 55 moves in the X1 direction, the control device 13 moves the grip pieces 59 and 60 of the holding mechanism 58 in directions away from each other. When the center position of the gripping pieces 59 and 60 in the X direction reaches the center in the longitudinal direction of the culture vessel 31, the control device 13 stops the rotation of the drive shaft 54. Thereby, the movement of the conveyance stand 55 in the X1 direction is stopped.

  After the movement of the transport base 55 in the X1 direction is stopped, the control device 13 moves the grip pieces 59 and 60 of the holding mechanism 58 in a direction in which they are brought closer to each other. Thereby, as shown in FIG. 5 (b), the culture vessel 31 is held between the gripping pieces 59 and 60. The culture container 31 is held by the holding mechanism 58 by sandwiching the culture container 31 by the gripping pieces 59 and 60. The control device 13 drives the motor 53 to raise the transport table 52 by a predetermined amount. As a result, the culture vessel 31 held by the holding mechanism 58 is lifted from the shelf 27a of the stocker 27. The control device 13 rotates the drive shaft 54 to move the transport base 55 in the X2 direction. Thereby, the culture container 31 is carried out from the storage position of the stocker 27. Then, when the culture vessel 31 held by the holding mechanism 58 reaches a position below the transport table 52, the control device 13 stops the rotation of the drive shaft 54. Thereby, the movement of the conveyance stand 52 stops (refer FIG.5 (c)).

  Thereafter, the control device 13 drives the motor 46. Thereby, the upper base plate 48 rotates in the R1 direction around the axis Z1. The control device 13 stops the driving of the motor 46 when the upper base plate 48 rotates 180 ° in the direction about the axis Z1. Thereby, the rotation of the upper base plate 48 is stopped.

  The control device 13 drives the motor 57 in conjunction with the driving of the motor 46. By driving the motor 57, the holding mechanism 58 rotates in the R2 direction around the axis Z2. When the holding mechanism 58 rotates 180 °, the control device 13 stops driving the motor 57. Thereby, the rotation of the holding mechanism 58 is stopped. That is, when the rotation operation of the upper base plate 48 in the R1 direction is started, the holding mechanism 58 is rotated in the R2 direction (the rotation direction of the holding mechanism 58 starts the upper base plate 48. When the rotation operation in the R1 direction is stopped, the rotation operation in the R2 direction of the holding mechanism 58 is also stopped, that is, the holding mechanism 58 rotates in the opposite direction to the rotation of the upper base plate 48. The rotation amount of the holding mechanism 58 during rotation is the same as the rotation amount of the upper base plate 48.

  After the rotation of the upper base plate 48 stops, the control device 13 rotates the drive shaft 54. Due to the rotation of the drive shaft 54, the transport table 55 moves in the X2 direction. Then, the control device 13 stops the rotation of the drive shaft 54 in response to the movement of the transport base 55 to above the container placement surface 28 a of the observation device 28. As a result, the movement of the transport table 55 in the X2 direction is stopped (see FIG. 6B). The control device 13 drives the motor 53 to lower the transport table 52. The descending amount of the transport table 52 is an amount corresponding to a gap generated between the lower surface of the culture vessel 31 and the vessel placement surface 28a of the observation device 28. The culture vessel 31 is placed on the vessel placement surface 28 a of the observation device 28 by the lowering of the transport table 52. Then, the control device 13 moves the gripping pieces 59 and 60 of the holding mechanism 58 in directions away from each other. In this state, the control device 13 drives the motor 53 to raise the transport table 52. Note that the amount by which the transport table 52 is raised at this time is the same amount as the amount by which the transport table 52 is lowered. Finally, the control device 13 rotates the drive shaft 54 and moves the transport base 55 in the X1 direction (see FIG. 6C). Accordingly, the culture container 31 is transported from the stocker 27 to the observation device 28 by the container transport device 29.

  A similar operation is performed when the culture vessel 31 is transported from the stocker 27 to the carrier 25. Further, when the culture container 31 is transported from the carrier 25 to the stocker 27, or when transported from the observation device 28 to the stocker 27, the reverse operation of the above-described operation is performed by the container transport device 29. That is, also in these operations, the holding mechanism 58 rotates in the opposite direction to the rotation of the upper base plate 48, and the rotation amount is the same as the rotation amount of the upper base plate 48.

  When the culture container 31 is transported by the container transport device 29 described above, the culture container 31 immediately after being unloaded from the stocker 27 has the side surface 31a on one end side in the longitudinal direction facing the stocker 27 and the side surface 31b on the other end side. Faces the observation device 28. Usually, when the upper base plate 48 is rotated 180 degrees in the R1 direction around the axis Z1, the side surface 31a of the culture vessel 31 faces the observation device 28 and the side surface 31b faces the stocker 27. Along with this rotation, the holding mechanism 58 is rotated by 180 ° about the axis Z2 in the R2 direction opposite to the R1 direction. For this reason, the culture vessel 31 after performing these rotation operations maintains the state in which the side surface 31a faces the stocker 27 and the side surface 31b faces the observation device 28, as before the rotation operation.

  Among these rotating operations, when the rotating operation of the upper base plate 48 in the R1 direction is performed, the cells (floating cells) floating in the culture solution of the culture vessel 31 are caused by the rotation of the upper base plate 48 around the axis Z1. Subject to moment of inertia. For this reason, when the rotation operation is stopped, the floating cells move in the culture solution. However, in the case of the present embodiment, the holding mechanism 58 is rotated by 180 ° in the R2 direction opposite to the R1 direction in conjunction with the rotation operation of the upper base plate 48 in the R1 direction. For this reason, in the floating cell 58, in addition to the moment of inertia caused by the rotation of the upper base plate 48 in the R1 direction, the moment of inertia caused by the rotation of the holding mechanism 58 in the R2 direction is generated. Moreover, since these moments of inertia are generated in opposite directions, these moments of inertia are canceled out. For this reason, the floating cells in the culture solution of the culture vessel 31 do not move and are kept in their original positions. Thereby, since generation | occurrence | production of the uneven distribution of a cell can be prevented, the cell in a culture container can be grown uniformly. Further, it does not affect the observation of cells such as the occurrence of a position where cells cannot be observed or a position where many cells can be observed.

  In this embodiment, although the example which has arrange | positioned the container conveyance apparatus 29 between the stocker 27 and the observation apparatus 28 is taken up, if it is a container conveyance apparatus which performs the linear operation | movement and rotation operation and conveys the culture container 31, The layout of the stocker 27, the observation device 28, and the container transport device in the temperature-controlled room need not be limited to this embodiment.

  DESCRIPTION OF SYMBOLS 10 ... Culture observation apparatus, 13 ... Control apparatus, 27 ... Stocker, 28 ... Observation apparatus, 29 ... Container conveyance apparatus, 31 ... Culture container, 46, 56 ... Motor, 47, 57 ... Drive shaft, 58 ... Holding mechanism

Claims (4)

A storage room for storing a plurality of culture containers in which cells are cultured;
An observation device for observing the cells cultured in the culture vessel;
The culture vessel is held in a state in which the culture vessel is held by a transport operation that combines a linear motion that moves the culture vessel in a horizontal direction and a rotational motion that rotates about an axis perpendicular to the horizontal direction of the culture vessel. A transfer device for transferring the storage from one of the storage and the observation device to the other;
Have
The transport device includes a first rotation mechanism that rotates in a direction opposite to the rotation direction of the rotation operation to maintain the posture of the culture vessel in a posture immediately after being held by the transport device. Characteristic culture observation device. In the culture observation apparatus according to claim 1,
The rotation amount in the first rotation mechanism is the same as the rotation amount during the rotation operation in the transport device,
The culture observation apparatus according to claim 1, wherein the rotation of the culture container in the first rotation mechanism is executed in accordance with a rotation operation of the transfer device. In the culture observation apparatus according to claim 1 or 2,
The transport device includes a second rotation mechanism that performs the rotation operation,
The culture observation apparatus, wherein the first rotation mechanism and the second rotation mechanism are provided independently of each other. In the culture observation apparatus according to any one of claims 1 to 3,
The transfer device
A holding unit for holding the culture vessel;
A moving mechanism for performing the linear motion;
Further comprising
The first rotation mechanism includes a mechanism for rotating the holding portion,
The culture observation apparatus, wherein the second rotation mechanism includes a mechanism that simultaneously rotates the moving mechanism and the second rotation mechanism.

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