WO2024154696A1 - Equipment for cell culture and cell culture method - Google Patents

Abstract

When performing cell culture and imaging in an incubator, a single object was observed by a microscope built into the incubator in the past. To observe multiple objects, installing separate movable units along an xyz direction was considered, but installation of such moving units is structurally difficult. Also, since the incubator had to be opened and closed and the built-in microscope operated each time for this same purpose, the risk of contaminating the cells was high and the cell culture efficiency was low. The present invention provides a cell culture device or culture method that permits cell culture of multiple cell culture vessels within a limited space and efficient periodic observation by imaging.

Description

Cell culture device and cell culture method

The present invention relates to a cell culture device and a cell culture method, and in particular to a structure and method for individually imaging cells in multiple cell culture vessels.

　The conventional observation method for observing cultured cells in an incubator involves placing cell culture vessels containing cells inside the incubator, and capturing images of each cell culture vessel at a specific time using a single imaging device.

The present invention aims to develop a cell culture device and a cell culture method that can efficiently perform cell culture in multiple cell culture containers within a given space and monitor the progress of the cultured cells by imaging.

Thus, the present invention provides the following:
(Item 1)
a plurality of stages for mounting cell culture vessels;
A drive unit that moves the stage in a direction including a vertical direction;
and a movable imaging unit configured to image cells in a cell culture vessel placed on the stage.
(Item 2)
2. The cell culture device according to claim 1, wherein the imaging unit is configured to image the cells in the cell culture vessel from below.
(Item 3)
2. The cell culture device according to claim 1, wherein the imaging unit is movable in the horizontal direction.
(Item 4)
The cell culture device according to any one of the preceding items, wherein each of the plurality of stages is configured to be capable of mounting a plurality of the cell culture vessels.
(Item 5)
The cell culture device according to any one of the preceding items, wherein at least one of the plurality of stages has a horizontal size of about 25 cm to about 35 cm in the long side direction and about 10 cm to about 20 cm in the short side direction.
(Item 6)
2. The cell culture device according to claim 1, wherein the imaging unit includes a cell observation device.
(Item 7)
2. The cell culture device according to claim 1, further comprising a control unit that controls the movement of the stages by the drive unit and the movement of the imaging unit.
(Item 8)
2. The cell culture device according to claim 1, further comprising a reader for reading an identification portion attached to the cell culture vessel.
(Item 9)
The control unit includes a receiving unit that receives an input of an imaging schedule for the cells in the cell culture vessel.
(Item 10)
The control unit controls the drive unit to move the stage, on which the cell culture vessel that is the subject of the imaging schedule is placed, to an imaging position in accordance with the imaging schedule, and controls the imaging unit to move and capture images of cells in the cell culture vessel that has been moved to the imaging position.
(Item 11)
2. The cell culture device according to claim 1, wherein the cell culture device is configured to be installed in an incubator.
(Item 12)
2. The cell culture device according to claim 1, wherein the driving unit is a rotor.
(Item 13)
a housing that accommodates the stage, the drive unit, and the imaging unit;
The cell culture device according to any of the preceding claims, further comprising a mechanism for controlling the cell culture environment within the housing.
(Item 14)
The cell culture device according to any of the above items, wherein at least one of the top, back and side of the housing is openable and closable, and a medium for cell culture can be replaced from at least one of the top, back and side.
(Item 15)
Any of the cell culture devices described above is configured to operate the drive unit for temperature equalization between the cell culture vessels in accordance with a schedule created based on the operation of the drive unit for imaging or operations on the cell culture vessels or the schedule for such operation.
(Item 16)
Placing a cell culture vessel containing cells on the stage of any one of the cell culture devices described above;
Culturing the cells; and
and capturing an image of the cells using the imaging unit.

The present invention makes it possible to efficiently perform cell culture in multiple cell culture vessels within a given space and monitor the progress of cultured cells through imaging.

FIG. 1 is a conceptual diagram showing a cell culture device 100 of the present invention and a stage 110 on which a cell culture vessel 1 is placed. FIG. 2 is a diagram showing the appearance of the cell culture device 100 and the cell culture vessel 1 according to the first embodiment of the present invention. FIG. 3 is a diagram showing the internal structure of the cell culture device 100 shown in FIG. FIG. 4A is a plan view showing the mechanism of the driving unit 120 that moves the stages 110a to 110d in the cell culture device 100 shown in FIG. FIG. 4B is a plan view corresponding to FIG. 4A when a planetary gear is used as the driving body. FIG. 5 is a plan view showing the mechanism by which the drive rotor 121a to which the stage 110 is attached rotates due to the rotation of the sun gear 122 attached to the rotating shaft 120a1 of the drive source (motor) 120a in the drive unit 120 shown in FIG. FIG. 6 is a diagram showing an example of a driving mechanism for moving the imaging unit 130 shown in FIG. FIG. 7 is a diagram showing a cell culture device 1001 equipped with a culture medium exchange mechanism 1010 as a first modification of the cell culture device 100 shown in FIG. 3, and shows its internal structure. FIG. 8 is a diagram showing a specific configuration of the culture medium exchange mechanism 1010 shown in FIG. FIG. 9 is a diagram showing an external appearance of an incubator-integrated cell culture device 1002 as a second modified example of the cell culture device 100 shown in FIG. FIG. 10 is a diagram showing an external appearance of a cell culture device 1003 that is integrated with an incubator and includes a culture medium exchange mechanism 1020, as a third modified example of the cell culture device 100 shown in FIG. FIG. 11 is a diagram showing an outline of the system of the cell culture device 100 shown in FIG. 3 and the operation unit 10 of the first modified example thereof. FIG. 12 is a diagram showing the operation of the cell culture device 100 shown in FIG. 3, illustrating the movement of the first stage 110a and the imaging section 130. In FIG. FIG. 13 is a diagram showing an outline of a system of a cell culture device 200 and its operation unit 20 according to the second embodiment of the present invention. FIG. 14 is a diagram showing the internal structure of a cell culture device 300 and the appearance of a cell culture vessel 3 according to the third embodiment of the present invention. FIG. 15 is a schematic diagram showing a mechanism for supporting a stage that uses members other than the rotating bodies (drive ring body and driven ring body) shown in FIG.

The present invention is described below. It should be understood that the terms used in this specification are used in the same manner as commonly used in the art unless otherwise specified. Therefore, unless otherwise defined, all technical and scientific terms used in this specification have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In the case of conflict, the present specification (including definitions) will take precedence.

In this specification, "about" means within a range of ±10% of the number that follows.

FIG. 1 is a conceptual diagram of a cell culture device 100 of the present invention, where FIG. 1(a) shows the structure of the cell culture device 100, and FIG. 1(b) shows an enlarged view of the stage 110 shown in FIG. 1(a).

It goes without saying that the shapes of the stage 110, drive unit 120, imaging unit 130, cell culture vessel 1, and device housing 100a shown in FIG. 1 are merely examples for explaining the present invention, and are not limited to those shown in the figure.

The present invention provides a cell culture device that can efficiently perform cell culture in a plurality of cell culture vessels and progress observation of the cultured cells by imaging within a given space. The cell culture device 100 includes:
As shown in FIG. 1( a ), a plurality of stages 110 for mounting cell culture vessels 1 ;
A drive unit 120 that moves the stage 110 in directions including the vertical direction;
The cell culture vessel 1 is provided on the stage 110. The cell culture vessel 1 is provided with a movable imaging unit 130 configured to capture an image of the cells in the cell culture vessel 1 mounted on the stage 110.

In this way, the cell culture equipment 100 of the present invention comprises a plurality of stages 110 on which the cell culture vessels 1 are placed, a drive unit 120 that moves the plurality of stages, and an imaging unit 130 that images the cells in the cell culture vessels 1 placed on the stages; as long as the drive unit 120 is capable of moving the stages 110 in directions including the vertical direction and the imaging unit 130 is movable, the other configurations are not limited and can be arbitrary.

This is because the cell culture equipment 100, which has the above-mentioned multiple stages 110, drive unit 120, and imaging unit 130, makes it possible to set the positional relationship between each of the multiple cell culture vessels 1 arranged in a specified space and the imaging unit 130 to a positional relationship suitable for photographing cells, and it becomes possible to image, i.e. observe, the cells in all of the cell culture vessels 1 using a small number (e.g., one) of imaging units 130 in the specified space.

(Imaging unit 130)
For example, the imaging unit 130 is preferably movable in the horizontal direction, although other configurations are not limited as long as it is movable. This is because, since the stage 110 is movable in directions including the vertical direction, if the imaging unit 130 is movable in the horizontal direction, it is possible to adjust the position of the imaging unit 130 so that the location where the cells are present in the cell culture vessel 1 arranged on the stage 110 can be appropriately imaged, and when multiple cell culture vessels 1 are arranged on each stage 110, it is possible to image all of the cell culture vessels 1 stored in the cell culture device 100 by adjusting the position of the imaging unit 130 with respect to each of the cell culture vessels 1. The imaging unit 130 may be movable in the vertical direction, and the operating mechanism in the vertical direction may be the same as or different from the operating mechanism in the horizontal direction. The vertical movement of the imaging unit 130 may be a movement for focusing, or may be a movement of a part of the imaging unit 130 (such as a lens). For example, an embodiment is envisaged in which the imaging unit 130 moves horizontally so as to be positioned below or above the cell culture vessel 1 being observed, and then the imaging unit 130 (or a part thereof) moves vertically to adjust its position (e.g., to adjust the focal depth) so as to properly image the observation target within the cell culture vessel 1.

Here, the imaging unit 130 is preferably configured to image the cells in the cell culture vessel 1 from below. This is because while imaging the cultured cells, the space above can be used for various operations for cell culture. In one embodiment, the imaging unit 130 may be configured to image the cells in the cell culture vessel 1 from above. When imaging from above the cell culture vessel 1, the image may be captured with the lid of the cell culture vessel 1 still attached, or without the lid (combined with a mechanism for opening the lid as necessary).

In addition, it is preferable that the imaging unit 130 includes a microscope that allows the subject to be observed at a magnified size. This is because the size of cultured cells is usually too small to be recognized by the naked eye, and so they must be magnified and imaged by the imaging unit.

In one embodiment, the imaging unit 130 can record the captured image. In one embodiment, the imaging unit 130 can transmit information about the captured image (including video). Information transmission may be by wire or wirelessly.

(Specific configuration of mechanism for moving imaging unit)
Here, the specific configuration of the drive mechanism for moving the imaging unit (imaging unit drive mechanism) is not limited and may be any configuration.

For example, in one embodiment, the imaging unit drive mechanism includes a guide rail provided on the bottom surface of the device housing 100a, wheels attached to the imaging unit, and a motor that drives the wheels, and the imaging unit is moved back and forth horizontally along the guide rail by rotating the wheels caused by the motor. Here, the motor may be built into the wheels, or may be attached to the housing of the imaging unit.

In another embodiment, the imaging unit drive mechanism includes a wire attached to the imaging unit housing, a pair of winding rollers attached to opposing side walls of the device housing 100a, and a motor for driving each roller, and selectively drives one or the other of the pair of winding rollers as appropriate to wind up one or the other end of the wire, thereby moving the imaging unit back and forth in the horizontal direction.

Furthermore, in other embodiments, the imaging unit drive mechanism includes a nut member attached to the housing of the imaging unit, a bolt member rotatably supported on the opposing side walls of the device housing 100a and screwed into the nut member, and a motor that rotates the bolt member, and the imaging unit is moved back and forth in the horizontal direction by the rotation of the bolt member by the motor.

(Stage 110)
The stage 110 is preferably configured to accommodate multiple cell culture vessels per stage, because such a configuration allows for parallel cell culture on a larger scale within the cell culture device, improving cell culture efficiency within a given space.

Furthermore, the size of the multiple stages 110 provided in the cell culture equipment is not specifically limited, but may typically have a horizontal size of about 25 cm to about 35 cm in the long side direction and about 10 cm to about 20 cm in the short side direction. Note that the horizontal size of the stage can be appropriately set by a person skilled in the art depending on the size that can be accommodated in a conventional incubator, the number of cell culture vessels 1 to be placed on one stage 110, the horizontal size of the cell culture vessels 1, etc., and therefore may be larger or smaller than the above horizontal size depending on the number of cell culture vessels 1 on the stage 110 or the horizontal size of the cell culture vessels 1.

(Drive unit 120)
The driving unit 120 may be any mechanism capable of moving the stage 110 in a direction including the vertical direction, such as a rotating body, a planetary gear, a worm gear, or a bevel gear.

In one embodiment, the driving unit 120 of the present invention includes a rotating body. The shape of the rotating body can be a disk, a ring, a gear, etc., but is not particularly limited. The rotational motion of the rotating body enables smooth movement of the stage on which the cell culture vessel 1 is placed within a limited space.

In one embodiment, the drive unit 120 of the present invention includes planetary gears. The planetary gears can reduce the rotation of the rotating shaft of the drive source (such as a motor) and transmit it to the rotating bodies (the driving rotor 121a and driven rotor 121b described below) that support the stage, and the stage that moves due to the rotation of the rotating bodies can be stopped at the desired position with greater precision using a simple configuration. Moreover, since the axis of the rotating shaft of the drive source and the axis of the rotating body that supports the stage coincide with each other, the structure is simplified. Note that the reducer that reduces the rotation of the rotating shaft of the drive source may be configured by combining gears other than planetary gears, and may, for example, include a worm gear that combines a worm and a worm wheel, or a bevel gear that combines conical frustum-shaped gears.

When using worm gears and bevel gears, the rotation axis of the drive gear and the rotation axis of the driven gear will intersect (for example, be perpendicular), which may be preferable depending on the shape of the housing of the cell culture equipment. Also, with worm gears, the rotation of the drive gear can be significantly slowed down, making it possible to stop the stage, which moves due to the rotation of the rotor, more accurately at the stopping position.

(Stage Support Mechanism)
The mechanism for supporting the stage is not limited to one using a rotating body (a ring-shaped disk member in FIG. 1(a)) rotatably attached to the equipment housing 100a as shown in FIG. 1(a), but may be, for example, one using a circular chain meshed with a sprocket, or one using multiple shelves included in a rack.

(Control unit 11)
The cell culture equipment 100 of the present invention preferably includes a control unit 11 that controls the movement of the multiple stages by the drive unit, the movement of the imaging unit, and imaging by the imaging unit. This is because, by simply instructing the control unit to image a specific cell culture vessel 1, the drive unit automatically moves the stage so that the cells in the specific cell culture vessel can be imaged by the imaging unit, and further, it becomes possible to move the imaging unit to an appropriate imaging position and to image the image by the imaging unit.

In other words, in this case, the cell culture device is equipped with a mutual communication function that receives external input, specifically, operation signals from the user or control signals from an external information device, and outputs information regarding the culture and imaging obtained by this cell culture device to the outside as the results of the culture, thereby performing culture and imaging based on operation information from the user and control information from a peripheral terminal, and making it possible to provide the results to the user or a peripheral terminal.

Here, the control unit 11 may include a receiving unit that receives input of an imaging schedule for the cells in the cell culture vessel 1. Alternatively, the control unit 11 may have a memory unit that stores information on the imaging schedule for the cells in the cell culture vessel 1.

For example, in one embodiment, the control unit 11 controls the drive unit 120 to move the stage 110, on which the cell culture vessel 1 to be imaged is placed, to an imaging position according to the imaging schedule described above, and then controls the imaging unit 130 to move and capture images of the cells in the cell culture vessel 1 that has been moved to the imaging position.

(Electromagnetic reader 140)
It is preferable that the cell culture equipment 100 further includes an electromagnetic reader 140 (see FIG. 3(a)) that reads an identification unit (e.g., an RF tag) attached to the cell culture vessel 1. This is because, by including this electromagnetic reader 140, the cell culture equipment 100 can identify all of the multiple cell culture vessels 1 contained in the cell culture equipment 100, and operations for each cell culture vessel 1, such as imaging the cultured cells, replacing or adding culture medium, and transmitting information about the cultured cells, can be performed. In this case, the control unit 11 may be capable of setting the observation time (i.e., imaging time) for each cell culture vessel 1, or may be capable of setting the imaging time for each stage 110.

In addition, the identifier may be an ID tag written in text instead of or in addition to an RF tag. In that case, the reader that reads the identifier is an image sensor (hereinafter also referred to as an OCR reader) with an optical character reading function instead of an electromagnetic reader. The identifier may include a bar code or a two-dimensional code.

(Incubator function)
The cell culture equipment 100 may be configured to be installed in an incubator, or the cell culture equipment 100 may itself have the function of an incubator (an integrated incubator).

For example, in one embodiment, the incubator-integrated cell culture device may further include, in addition to the above-mentioned stage 110, drive unit 120, and image capture unit 130, a device case (housing) 100a that houses them, and a mechanism (not shown, which may be a control unit 11) for controlling the cell culture environment (temperature, humidity, carbon dioxide concentration, etc.) in the housing 100a. In this case, it is preferable that the upper part of the housing 100a is openable and closable, so that operations such as changing the culture medium for cell culture can be performed from the upper part. In other words, in the cell culture device 100 that houses the cell culture vessel 1 in the housing, operations on the cell culture vessel 1 on the stage 110 located at the top end are easier than operations on the cell culture vessel 1 on the stage 110 located at other positions, so it is preferable that the upper part of the housing is openable and closable.

(Temperature effect)
It is preferable that the same cells cultured under the same conditions or in the same incubator show similar growth. Since the culture temperature is one of the factors that affect cell growth, it is preferable that the temperature applied to the cell culture vessel is kept uniform in order to increase the reproducibility of cell growth during culture, and it is preferable that the temperature difference due to the difference in the installation position of the cell culture vessel in the incubator is small. Since the cell culture device described herein can move the cell culture vessel in the incubator with the operation of the drive unit, it is expected that even if there is a variation in the temperature distribution in the incubator, the cell culture vessel is less affected by it. In addition, since the cell culture device described herein moves the drive unit and the imaging unit in the incubator, it is considered that the air in the incubator is naturally stirred accordingly, and the temperature in the incubator can be kept uniform even without an additional air stirring mechanism (propeller, blower pump, etc.). In one embodiment, the cell culture device described herein may be equipped with a sensor for sensing the temperature in the incubator. In one embodiment, the cell culture device described herein may be equipped with multiple sensors for sensing the temperature in the incubator at different positions. The inventors have found that the level of cell growth may vary in response to temperature differences between positions in an incubator that cannot be accurately detected by conventional incubator temperature sensors. Therefore, in one embodiment, in the cell culture device described herein, the driving unit may be operated independently of the sensed incubator temperature. However, this does not mean that the present specification excludes an embodiment in which the driving unit is operated in response to the sensed incubator temperature.

In one embodiment, the cell culture device described herein is configured to operate the drive unit according to a schedule (temperature equalization schedule) for temperature equalization between the cell culture vessels. Here, "temperature equalization" does not require that the temperature applied to the cell culture vessels be completely uniform, but means that the temperature variation applied to the cell culture vessels is reduced, which can reduce the variation in the results of cell culture. In one embodiment, the temperature equalization schedule is created based on the operation of the drive unit or a schedule thereof. The cell culture device described herein can observe the target cells by operating the drive unit, and can perform and schedule operations on the cell culture vessels (changing the culture medium for the target cells and/or removing the cell culture vessels). Therefore, when such a drive unit is operated, the position of the cell culture vessel in the incubator is changed, and the temperature exposed between the cell culture vessels is equalized, but it is preferable that an additional operation to change the position of the cell culture vessel is performed during a time when such a drive unit is not operated. The drive unit may also be operated to read an identification unit attached to the cell culture vessel by an electromagnetic reader at a predetermined position. For example, when there is no long-term imaging schedule, a temperature equalization schedule for the next operation of the drive unit may be created based on the temperature equalization schedule. In one embodiment, the temperature equalization schedule includes operating the drive unit a certain time (e.g., 30 minutes, 1 hour, 2 hours, 3 hours, 6 hours, 12 hours, 24 hours, 36 hours, 48 hours, etc.) after the operation or scheduled operation of the drive unit. In one embodiment, the temperature equalization schedule may be set for each cell culture vessel. For example, when the cell culture vessel A and the cell culture vessel B are housed in the same incubator, a temperature equalization schedule may be created for each of the cell culture vessel A and the cell culture vessel B, and these may be registered together on one operation schedule of the drive unit of the incubator. In one embodiment, the temperature equalization schedule includes operating the drive unit a certain time (e.g., about 30 minutes, 1 hour, 2 hours, 3 hours, 6 hours, 12 hours, 24 hours, 36 hours, 48 hours, etc.) before the scheduled operation of the drive unit. In one embodiment, actuation of the drive for temperature equalization between the cell culture vessels can be about 30°, 60°, 90°, 120°, 150°, 180°, 210°, 240°, 270°, 300°, 330°, or 360° rotation of the drive. The rotation direction of the drive for temperature equalization between the cell culture vessels can be fixed or selected (e.g., based on the current position relative to a reference position, or based on the previous actuation of the drive or its planned rotation direction).

The control unit 11 can create and store a temperature equalization schedule. The control unit 11 manages information (such as an imaging schedule) related to the operation of the cell culture device described in this specification, so that a temperature equalization schedule can be easily created based on the information stored in the control unit.

(Mechanism for medium exchange)
Furthermore, regardless of whether the cell culture equipment 100 is a type that is installed in an incubator or a type that is integrated with an incubator, it is preferable that the cell culture equipment 100 has a mechanism for medium exchange. This is because the provision of the mechanism for medium exchange allows cell culture to be completed within the cell culture equipment. The mechanism for medium exchange includes a means for supplying medium to the cell culture vessel 1 and a means for discharging the medium from the cell culture vessel 1. The means for supplying medium and the means for discharging medium may share some members (e.g., members that serve as a medium outlet and a suction port). The mechanism for medium exchange may include a means for removing the lid of the cell culture vessel 1.

In one embodiment, the mechanism for medium replacement is attached to the top of the cell culture device 100 and replaces the medium in the cell culture vessel 1 on the stage 110 located at the top end. The mechanism for medium replacement may be movable within the cell culture device 100, and may be movable in the horizontal direction, for example, so that the medium in multiple cell culture vessels 1 on the stage 110 can be replaced. In one embodiment, the mechanism for medium replacement may be movable in the vertical direction (as well as in the horizontal direction, if necessary), and may adjust its positional relationship with the medium liquid (or its surface) in the cell culture vessel 1 when aspirating and/or adding the medium.

The mechanism for medium replacement may have a pipette or dropper structure, or may have a structure that allows for the attachment and detachment of disposable tips.

The cell culture equipment 100 of the present invention may also include a mechanism for placing the cell culture vessel 1 on the stage 110 and/or a mechanism for removing the cell culture vessel 1 from the stage 110, and these mechanisms may be in the form of a belt conveyor for transporting the cell culture vessel 1, a robot arm, or the like. The transport of the cell culture vessel 1 by these mechanisms may be linked to the movement of the stage as an object of control by the control unit 11, for example. With these mechanisms, the cell culture equipment 100 of the present invention can further promote the automation of cell culture.

The cell culture method of the present invention uses the cell culture device 100 described above, and as long as it includes placing a cell culture vessel 1 containing cells on the stage 110 of the cell culture device 100, culturing the cells, and imaging the cells with the imaging unit 130, other configurations are not limited and can be arbitrary.

The reason is that the cell culture method of the present invention uses the cell culture equipment 100 of the present invention, and when cell culture vessels 1 are placed on each of the multiple stages 110 to culture and image the cells, the relative position of any cell culture vessel 1 and the imaging section 130 can be set to a relative position suitable for imaging in which any cell culture vessel 1 is located close to and on the imaging section 130 by vertically moving the multiple stages 110 and horizontally moving the imaging section 130, and the cells in any cell culture vessel 1 can be imaged at an appropriate imaging position with a single imaging section 130.

As described above, the cell culture equipment 100 of the present invention comprises a plurality of stages 110 on which the cell culture vessels 1 are placed, a drive unit 120 that moves the plurality of stages 110, and an imaging unit 130 that images the cells in the cell culture vessels 1 placed on the stages 110. As long as the drive unit 120 can move the stage 110 in directions including the vertical direction and the imaging unit 130 is movable, other configurations are not limited, but in the following embodiment, the cell culture equipment 100 comprises a plurality of stages 110, a drive unit 120, and an imaging unit 130, the drive unit 120 includes a rotor, the imaging unit 130 is movable in the horizontal direction, and is configured to image the cells in the cell culture vessels 1 from below.

In particular, embodiment 1 (FIGS. 2 to 6, 11 to 12) illustrates a cell culture device 100 that is installed inside an incubator.

In the first modified example of the first embodiment (FIGS. 7 and 8), the cell culture device 1001 is the cell culture device 100 of the first embodiment, which is equipped with a culture medium exchange mechanism 1010.

In the second modification of the first embodiment (FIG. 9), the cell culture device 1002 is an incubator-integrated version of the cell culture device 100 of the first embodiment.

In the third modification of the first embodiment (FIG. 10), the cell culture device 1002 of the second modification of the first embodiment is provided with a culture medium exchange mechanism 1020.

In embodiment 2 (FIG. 13), the cell culture device 200 is the cell culture device 100 of embodiment 1, which is configured to perform culture medium replacement according to the culture medium replacement schedule and culture status.

In embodiment 3 (FIG. 14), the cell culture device 300 is provided with a stage 310 and a cell culture container 3, which are different in structure from the stage 110 and the cell culture container 1 in the cell culture device 100 of embodiment 1, respectively.

Another embodiment (Figure 15) is a stage support mechanism with a different configuration from the stage support mechanisms in embodiments 1 to 3.

Below, an embodiment of the present invention will be described with reference to the drawings. In the following description of embodiment 1 and its modified examples (FIGS. 2 to 12), the same reference numerals are used to denote the cell culture device 100, stage 110, drive unit 120, imaging unit 130, cell culture vessel 1, and control unit 11 shown in FIG. 1.

(Embodiment 1)
2A and 2B are diagrams showing a cell culture device 100 according to embodiment 1 of the present invention, in which FIG. 2A shows the appearance of the cell culture device 100, FIG. 2B shows an enlarged view of the appearance of the cell culture vessel 1 shown in FIG. 2A, and FIG. 2C shows the cell culture vessel 1 shown in FIG. 2A with the lid open.

As shown in FIG. 2(a), the cell culture equipment 100 has an equipment case (housing) 100a and a stage 110 arranged inside the housing 100a so as to be movable up and down. Here, the stage 110 is a holder that holds a cell culture vessel 1 placed thereon. The cell culture vessel 1 is specifically a petri dish (FIG. 2(b)), and is composed of a petri dish body 1a that contains culture medium and cells, and a petri dish cover 1b (FIG. 2(c)). Furthermore, if the cell culture equipment 100 is a type that is to be installed inside an incubator, it is preferable that the housing 100a is composed of a cylindrical body with openings on the front and back so that the culture environment inside the incubator is effectively reflected inside the cell culture equipment 100.

The internal structure of the cell culture device 100 will now be described in detail.
3A and 3B are diagrams showing the specific configuration of the cell culture equipment 100 shown in FIG. 2(a), in which FIG. 3A shows its internal structure, FIG. 3B shows the structure of the stage 110 in FIG. 3(a) viewed from above, and FIG. 3C shows the structure of the stage 110 in FIG. 3(a) viewed from below.

Note that in FIG. 3(a), the first through fourth stages are shown as stages 110a through 110d, but when there is no need to distinguish between the stages, these four stages 110a through 110d are all shown as stage 110, as shown in FIG. 2(a).

As shown in FIG. 3(a), the cell culture device 100 of this embodiment includes a first to fourth stages 110a to 110d for mounting the cell culture vessel 1, a drive unit 120 for moving these stages 110a to 110d in directions including the vertical direction (up and down on the page), and a movable imaging unit 130 configured to capture images of cells in the cell culture vessel 1 mounted on each of the stages 110a to 110d. The configuration of each unit is described in detail below.

(Stage 110)
As shown in FIG. 3B, the stage 110 (110a to 110d) has a container mounting table 1101 and a support shaft portion 1102, and the container mounting table 1101 is connected to the drive unit 120 of the cell culture device 100 by the support shaft portion 1102. As shown in FIG. 3C, the container mounting table 1101 has an opening 1101a that allows the cell culture container (specifically, a petri dish) 1 mounted thereon to be observed from below. Note that the container mounting table 1101 is not limited to one having the opening 1101a, and may have any configuration that allows the cells in the cell culture container 1 mounted on the stage 110 to be imaged by the imaging unit 130 arranged below the stage 110, such as one made of a transparent material (for example, a transparent resin such as acrylic) instead of having the opening 1101a. Also, the petri dish as the cell culture container 1 is typically made of a transparent material such as glass, acrylic resin, or polystyrene.

Here, the driving unit 120 rotates the multiple stages 110 around one horizontal axis, and the stages 110 are attached to the driving unit 120 so that the mounting surface of the container mounting table 1101 (the surface on which the cell culture equipment 100 is placed) always faces vertically upwards, regardless of the rotational position of the stages 110.

The multiple stages 110 (specifically, the container mounting table 1101) may have a horizontal size of, for example, about 25 cm to about 35 cm in the long side direction and about 10 cm to about 20 cm in the short side direction. The multiple stages 110 may all be the same size, or may be different sizes.

The support shaft portion 1102 is a rod-shaped member (e.g., a round bar, a square bar, etc.) made of a hard resin material such as acrylic resin or polyvinyl chloride, or a metal material such as stainless steel, and is rotatably attached to the rotors of the drive portion 120 (specifically, the drive rotor 121a and the driven rotor 121b described below).

(Drive unit 120)
As shown in FIG. 3(a), the driving unit 120 has a driving rotor 121a rotatably supported on one of the opposing side walls of the equipment housing 100a of the cell culture equipment 100, and a driven rotor 121b rotatably supported on the other opposing side wall, and the driving rotor 121a and the driven rotor 121b are connected by four stages 110a to 110d and/or a central shaft 126 so that they rotate together.

FIG. 4A is a plan view showing the specific configuration of the drive unit 120 shown in FIG. 3(a) when viewed from direction B in FIG. 3(a). FIG. 4A(a) shows the drive rotor (disk body in this case) 121a in the drive unit 120, and FIG. 4A(b) shows the driven rotor 121b in the drive unit 120.

In a further embodiment, the drive unit 120 includes a planetary gear and is equipped with a motor 120a as a drive source and a reduction gear 120b that reduces the rotation of the rotating shaft 120a1 (see FIG. 4B(a)) of the motor 120a and transmits it to the drive rotor (here, a ring body) 121a.

The reduction gear 120b shown in FIG. 4B(a) has a sun gear 122 attached to the rotating shaft 120a1 of the motor 120a, four planetary gears 123 that mesh with the sun gear 122, and an internal gear 124 that meshes with the four planetary gears 123. Here, the sun gear 122 is positioned inside the internal gear 124, and the four planetary gears 123 are provided between the sun gear 122 and the internal gear 124 so as to mesh with these gears 122 and 124.

In this reduction gear 120b, the internal gear 124 is fixed to the side wall 100a1 of the device housing 100a, and when the sun gear 122 rotates as a power gear, the planetary gear 123 revolves between the internal gear 124 and the sun gear 122, i.e., around the sun gear 122, in the same direction as the rotational direction of the sun gear 122, and the revolution force of the planetary gear 123 is transmitted as a rotational force to the drive rotor 121a by the connecting member 123a.

Note that, here, a reduction gear using planetary gears is illustrated in which the revolution force of the revolving planetary gear 123 is transmitted to the driving rotor 121a by the connecting member 123a, but a reduction gear using planetary gears may also be configured such that the planetary gear 123 has its rotation axis fixed so that it only rotates on its axis and does not revolve, and the internal gear 124 is integrated with the driving rotor 121a so that it can rotate. In this case, the connecting member 123a that transmits the revolution force of the planetary gear 123 to the driving rotor 121a is not necessary.

The driven rotor 121b is connected to the driving rotor 121a by the stage 110 as shown in FIG. 3(a), and is rotatably held by three support rollers 125 attached to the side wall 100a2 of the device housing 100a as shown in FIG. 4B(b). Therefore, the driven rotor 121b rotates together with the driving rotor 121a by transmitting the rotational force of the driving rotor 121a to the driven rotor 121b via the stage 110 (support shaft 1102 and container mounting table 1101). Even when the container mounting table 1101 moves with the rotation of the driving ring body 121a, it is preferable that the container mounting surface always faces vertically upward, so that the support shaft 1102 can be configured to rotate without being fixed to the container mounting table 1101 or the driving ring body 121a. In this case, by positioning the center of gravity of the container mounting table 1101 on its back surface, it is possible to encourage the front surface, that is, the container mounting surface, to face upward.

FIG. 5 is a plan view showing the connection relationship between the sun gear 122, planetary gear 123, internal gear 124, driving rotor 121a, and connecting member 123a in the reduction gear 120b shown in FIG. 4B(a). FIG. 5(a) shows the sun gear 122 attached to the rotating shaft portion 120a1 of the driving source 120a and the internal gear 124 fixed to the side wall 100a1 of the device housing 100a. FIG. 5(b) shows the planetary gear 123 that revolves around the sun gear 122 and the driving rotor 121a connected to the planetary gear 123. FIG. 5(c) shows the state in which the planetary gear 123 is assembled between the sun gear 122 and the internal gear 124.

As shown in FIG. 5(a), the sun gear 122 is attached to the rotating shaft 120a1 of the drive source 120a, and the internal gear 124 is fixed to the side wall 100a1 of the device housing 100a of the cell culture device 100.

As shown in FIG. 5(b), the rotation shafts 123b of the four planetary gears 123 are connected to the driving rotor 121a by a connecting member (planet carrier) 123a. Here, the connecting member 123a is rotatably connected to the rotation shafts 123b of the four planetary gears 123 so that it rotates on its own axis due to the revolution of the planetary gears 123. Furthermore, the connecting member 123a is connected to the driving rotor 121a so that the rotation of the connecting member 123a causes the driving rotor 121a to rotate around an axis that coincides with the rotation axis of the sun gear 122.

The specific configuration of the connecting member 123a shown as the planetary carrier in Figures 4B(a) and 5(b) is not limited to that shown (a cross-shaped structure), and may be anything that can transmit the revolution force of the planetary gear 123 as a rotational force to the driving rotor 121a.

When the planetary gear 123 shown in FIG. 5(b) is assembled between the sun gear 122 and the internal gear 124 shown in FIG. 5(a), a reduction gear 120b is obtained in which the planetary gear 123 performs planetary motion between the sun gear 122 and the internal gear 124, as shown in FIG. 5(c).

In this reduction gear 120b, as shown in FIG. 4B(a), when the sun gear 122 rotates due to the rotation of the drive source (specifically, the motor) 120a, the drive rotor 121a rotates by receiving the revolution force of the planetary gear 123, which rotates in the opposite direction to the rotation of the sun gear 122 and revolves in the same direction as the rotation of the sun gear 122, via the connecting member 123a. In this case, the relationship between the angle at which the planetary gear 123 rotates on its own axis and the angle at which it rotates due to its own rotation is such that the angle at which it rotates on its own axis and the angle at which it rotates due to its own rotation are smaller than the angle at which it rotates due to its own rotation (about 1/2 in FIG. 4B(a)), so that the resolution of the rotation angle control of the drive rotor 121a can be made higher than the resolution of the rotation angle control of the drive source 120a. By changing the size of the member, the resolution of the rotation angle control of the drive rotor 121a can be changed as appropriate.

As shown in FIG. 3(a) and FIG. 4B(b), the driven rotor 121b is placed on three support rollers 125 attached to the side wall 100a2 of the device housing 100a of the cell culture device 100 and is rotatably supported by these support rollers 125. Since the driven rotor 121b and the driving rotor 121a are connected by the stage 110, the driven rotor 121b receives the rotational force of the driving rotor 121a via the stage 110 and rotates integrally with the driving rotor 121a.

As a result, in this reduction gear 120b, the stage 110 connecting the driving rotor 121a and the driven rotor 121b is rotated with a higher resolution of rotation angle control than the resolution of the rotation angle control of the rotating shaft 120a1 of the driving source 120a (in other words, the sun gear 122), thereby improving the accuracy of stopping the stage 110 at a specified rotation position.

(Imaging unit 130)
In the cell culture device 100, the imaging unit 130 uses a microscope so as to be able to magnify and image the cells in the cell culture vessel 1 to be imaged. As shown in Fig. 4(a) , the imaging unit 130 is disposed on the bottom surface of the device housing (device housing of the cell culture device 100) 100a so as to image the cells in the cell culture vessel 1 placed on the stage 110 from below the cell culture vessel 1.

Furthermore, the imaging unit 130 is configured to be movable in the horizontal direction, specifically, in the arrangement direction of the multiple cell culture vessels 1 arranged on the stage 110, that is, in the direction along the rotation axes of the driving rotor 121a and the driven rotor 121b.

The driving unit that moves the imaging unit 130 is not limited and can be any type.

The mechanism of the drive unit that moves the imaging unit 130 (imaging unit drive mechanism) will be described below.
Fig. 6 is a diagram showing a specific example of an imaging unit drive mechanism, and shows an imaging unit moving mechanism seen from a cross section corresponding to the X-X cross section of Fig. 3(a). In particular, Fig. 6(a) shows a mechanism for attaching wheels to the imaging unit and moving it on a guide rail, Fig. 6(b) shows a mechanism for moving the imaging unit 130 by pulling it with a pair of wires, and Fig. 6(c) shows a mechanism for attaching a nut member to the imaging unit 130 and rotating a bolt member screwed into the nut member to move the imaging unit 130.
Specifically, the imaging unit drive mechanism 130a shown in Fig. 6(a) includes a pair of opposing guide rails 131a provided on the bottom surface of the device housing 100a, four wheels 131b attached to the imaging unit 130, and a motor 131c for driving at least one of the wheels 131b, and is configured so that the imaging unit 130 moves back and forth horizontally on the guide rails 131a by the rotation of the wheels 131b by the motor 131c. Here, the motor 131c may be attached to the housing of the imaging unit 130 as shown in Fig. 6(a) or may be built into the wheels.

The imaging unit drive mechanism 130b shown in FIG. 6(b) includes a pair of wires 131b and 132b attached to opposing sides of the housing of the imaging unit 130, and a pair of electric rollers 133b and 134b attached to opposing side walls of the device housing 100a, and is configured to move the imaging unit 130 back and forth in the horizontal direction by selectively driving one or the other of the pair of electric rollers 133b and 134b as appropriate and winding up the wires 131b and 132b connected to each of them.

Furthermore, the imaging unit drive mechanism 130c shown in FIG. 6(c) includes a nut member 132c attached to the housing of the imaging unit 130, a bolt member 131c rotatably supported by the opposing side walls of the device housing 100a and screwed into the nut member 132c, and a motor (not shown) that rotates the bolt member 131c, and is configured so that the imaging unit 130 moves back and forth in the horizontal direction as the nut member 132c moves due to the rotation of the bolt member 131c. Here, both ends of the bolt member 131c are rotatably supported by bearings 133c and 133d attached to the opposing side walls of the device housing 100a. The motor that rotates the bolt member 131c may be built into the bearing, or may be provided in the device housing 100a separately from the bearing.

(Electromagnetic reader 140)
The cell culture device 100 further includes a reader 140 that reads the container identification unit attached to the cell culture container 1, and is configured to be able to identify all the cell culture containers 1 placed on the multiple stages 110. Here, the reader 140 is provided on the upper surface of the imaging unit 130. The container identification unit is a part that indicates an identification ID for identifying each individual cell culture container 1, and is provided, for example, on the bottom surface of the cell culture container 1 so that it can be read by the reader 140. Specifically, this container identification unit may be an RF tag, may indicate the identification ID by a barcode, or may indicate the identification ID by a two-dimensional code. However, when an RF tag is used for the container identification unit, an electromagnetic reader is used as the reader, and when a barcode or two-dimensional code is used for the container identifier, a barcode reader or a two-dimensional code reader is used as the reader.

The container identifier may also be an ID tag written in characters. In this case, a reader equipped with an OCR function (optical character recognition function) (OCR reader) is used. The OCR reader may be the imaging unit 130. This OCR reader acquires the characters written on the ID tag as image information. In this case, in addition to analysis to extract character information by processing such as pattern recognition of the image information acquired by the OCR reader (the analysis may be performed in the OCR reader or another analysis device may be used), it is also possible to detect information on the culture status, such as the shape of the cells and the color of the culture medium, and associate it with the ID information, and by tracking the culture status in each cell culture container from moment to moment, it is also possible to perform culture medium replacement and feedback control of the culture conditions.

The reader 140 may not only read the container identification unit attached to the cell culture vessel 1, but also read the stage identification unit attached to each stage 110. Here, the stage identification unit indicates an identification ID that identifies each individual stage 110 (e.g., an RF tag, a barcode, a two-dimensional code, an ID tag written in text, etc.). In this case, the cell culture equipment 100 can recognize which cell culture vessel 1 is placed on which stage 110. Furthermore, each stage 110 may have an area identification unit that identifies each of a plurality of areas (container placement areas) in which the cell culture vessel 1 is placed.

The cell culture device 100 of the above-mentioned embodiment 1 may have a mechanism for exchanging the culture medium contained in the cell culture vessel 1 (culture medium exchange mechanism), and a cell culture device 1001 having this culture medium exchange function will be described below as modified example 1 of embodiment 1.

(First Modification of First Embodiment)
FIG. 7 is a diagram showing a cell culture device 1001 equipped with a culture medium exchange mechanism 1010 as a first modification of the cell culture device 100 shown in FIG. 3(a), and shows its internal structure.

As shown in FIG. 7, the cell culture device 1001 according to this modified example 1 is equipped with a culture medium exchange mechanism 1010 for exchanging the culture medium contained in each cell culture vessel 1 in the cell culture device 100 according to embodiment 1.

Figure 8 shows the specific configuration of the culture medium exchange mechanism 1010 shown in Figure 7, where Figure 8(a) shows the structure of the culture medium exchange mechanism 1010 viewed from diagonally above, Figure 8(b) shows the structure of the culture medium exchange mechanism 1010 viewed from diagonally below, Figure 8(c) shows the lid opening/closing member 103, Figure 8(d) shows the operation of the lid opening/closing member 103, and Figure 8(e) shows the operation of the culture medium supply pipe 102a and the culture medium discharge pipe 102b.

As shown in FIG. 8(a), the culture medium exchange mechanism 1010 has a culture medium supply pipe 102a, a culture medium discharge pipe 102b, a lid opening/closing member 103, and a guide member 1010a that holds them so that they can be moved horizontally. In one embodiment, an arm or actuator is attached to the guide member 1010a, which moves at least one of the culture medium supply pipe 102a, the culture medium discharge pipe 102b, and the lid opening/closing member 103 to a predetermined position. In one embodiment, a guide groove is formed on the underside of the guide member 1010a, along which a member can be slid and moved. An arm or actuator may be attached to the guide groove to further move the member. In one specific embodiment, as shown in FIG. 8(b), first to third guide grooves 1011 to 1013 are formed in parallel on the underside of the guide member 1010a, with the cover opening/closing member 103 slidably attached to the second guide groove 1012 in the center, the culture medium supply pipe 102a slidably attached to the first guide groove 1011 on one side of the guide member 1010a, and the culture medium discharge pipe 102b slidably attached to the third guide groove 1013 on the other side.

Here, the culture medium supply pipe 102a is a pipe for supplying the culture medium L to the cell culture vessel 1, and is configured to send the culture medium L to the cell culture vessel 1. The culture medium discharge pipe 102b is a pipe for discharging the culture medium L from the cell culture vessel 1, and is configured to suck the culture medium L from the cell culture vessel 1.

In one embodiment, the medium supply pipe 102a and the medium discharge pipe 102b may be connected to a fluid-connected tube. In one embodiment, the medium supply pipe 102a and the medium discharge pipe 102b may have an expandable structure, specifically, a structure that shrinks during sliding so as not to interfere with the cell culture vessel 1 on the stage 110 located at the upper end, and extends to reach the inside of the cell culture vessel 1 during medium supply or medium discharge.

The lid opening/closing member 103 also includes an adsorption portion 103a and a support rod 103b. The lower end of the support rod 103b supports the adsorption portion 103a, which is adsorbed to the dish lid member 1b of the dish, which is the cell culture vessel 1, and the upper end of the support rod 103 is slidably supported in the second guide groove 1012.

In the culture medium exchange mechanism 1010 configured as described above, as shown in FIG. 8(c), the suction portion 103a of the lid opening/closing member 103 suctions the petri dish lid member 1b, and as shown in FIG. 8(d), the petri dish lid member 1b is lifted to create a gap between the petri dish body 1a and the petri dish lid member 1b. In one embodiment, the petri dish lid member 1b may be retracted from directly above the petri dish body 1a. In this state, the culture medium supply pipe 102a and the culture medium discharge pipe 102b are moved inside the petri dish body 1a so as to avoid the petri dish lid member 1b, and one of them, for example, the culture medium supply pipe 102a, is extended as shown in FIG. 8(e), so that the culture medium L can be supplied into the petri dish body 1a. The culture medium can also be discharged using the culture medium discharge pipe 102b in the same manner as the culture medium is supplied.

In addition, in the above-mentioned embodiment 1 and its modified example 1, the cell culture device 100 is a type that can be placed in an incubator, but the cell culture device may be integrated with the incubator, and an incubator-integrated cell culture vessel will be described below as modified example 2 of embodiment 1.

(Modification 2 of the First Embodiment)
FIG. 9 is a diagram showing an incubator-integrated cell culture device 1002 as a second modified example of the cell culture device 100 shown in FIG. 3(a), and shows its external appearance.

As shown in FIG. 9, the cell culture device 1002 of the second modified example is the cell culture device 100 of the first embodiment, which has a closed device housing 100b instead of the open device housing 100a, and further has an environment forming system (not shown) that forms a cell culture environment similar to an incubator. Here, factors that form the cell culture environment include temperature, humidity, carbon dioxide concentration, oxygen concentration, and light exposure.

In this case, a cell culture environment similar to that of an incubator is formed inside the device housing 100b of the cell culture device 1002 of variant example 2, making it possible to perform cell culture using only the cell culture device 1002 without the need for a separate incubator. In this way, the incubator-integrated cell culture device 1002 can communicate the cell culture environment and culture results without requiring additional communication equipment for information sharing between the incubator and the cell culture device.

Furthermore, in the incubator-integrated cell culture equipment 1002, a separate cell culture environment can be set for each individual cell culture equipment 1002. Therefore, when multiple cell culture equipment 1002 are used, a more diverse range of cell culture is possible compared to a case where multiple cell culture equipment 100 are housed in a single incubator and cells are cultured in a common cell culture environment for the multiple cell culture equipment 100.

Furthermore, in this incubator-integrated cell culture device 1002, it is preferable to have an opening 101 that can be opened and closed by a top cover 101a at the top of the device housing 100b. Since the interior of this type of cell culture device 1002 is sealed, by providing the device housing 100b with an opening 101 that can be opened and closed by a top cover 101a, it becomes possible to insert and remove the cell culture container 1 into and from the device housing 100b without significantly changing the culture environment inside the device housing 100b.

Furthermore, it is preferable that the incubator-integrated cell culture device 1002 also has a culture medium replacement mechanism, and such a cell culture device will be described below as Variation 3 of Embodiment 1.

(Variation 3 of the First Embodiment)
FIG. 10 is a diagram showing an external appearance of a cell culture device 1003 that is integrated with an incubator and includes a culture medium exchange mechanism 1020, as a third modified example of the cell culture device 100 shown in FIG. 3(a).

The cell culture device 1003 according to the third modification of the first embodiment is configured by providing a culture medium replacement mechanism 1020 to the cell culture device 1002 according to the second modification described above.
This culture medium exchange mechanism 1020 has substantially the same configuration as the culture medium exchange mechanism 1010 in a cell culture device 1001 ( FIG. 7 ) that is to be installed in an incubator, and is provided with a culture medium supply pipe 102a that supplies culture medium to the cell culture vessel 1 placed on the stage 110 from the outside of the device casing 100b through an opening 101 that can be opened and closed by a top lid 101a, and a culture medium discharge pipe 102b that discharges the culture medium from the cell culture vessel 1 placed on the stage 110 from the outside of the device casing 100b through the opening 101 that can be opened and closed by a top lid 101a.

Here, the culture medium supply pipe 102a, the culture medium discharge pipe 102b, and the lid opening/closing member 103 are the same as those in the second variation of the first embodiment, but the guide member 1020a differs from the guide member 1010a in the first variation of the first embodiment in that the guide member 1020a is supported by a specific mechanism (not shown) so as to be horizontally movable relative to the device housing 100b so as not to interfere with the top lid 101a when the top lid 101a is opened or closed.

In the above-mentioned embodiment 1 and its variations 1 to 3, a petri dish is shown as the cell culture vessel 1, but the structure of the cell culture vessel 1 is not limited, and any shape is acceptable as long as it can be placed on the stage 110.
Next, the operation unit 10 of the cell culture device 100 according to the first embodiment and the operation unit of the cell culture device 1001 according to the first modified example of the first embodiment will be described.

As described above, the cell culture device 100 of embodiment 1 does not have a culture medium exchange mechanism 1010, and the cell culture device 1001 of modified example 1 of embodiment 1 is the cell culture device 100 of embodiment 1 equipped with a culture medium exchange mechanism 1010. Therefore, the operation unit 10 of the cell culture device 100 of embodiment 1 and the operation unit 10 of the cell culture device 1001 of modified example 1 of embodiment 1 have different detailed configurations.

(Operation Unit 10)
The cell culture equipment 100 of embodiment 1 is equipped with an operation unit 10 including a control unit 11 that controls the movement of the stage 110, the movement of the imaging unit 130, and the imaging of cells by the imaging unit 130. The configuration of this operation unit 10 will be described in detail below.

FIG. 11 shows an example of the configuration of the operation unit 10 included in the cell culture device 100 shown in FIG. 3(a), FIG. 11(a) is a block diagram showing the configuration of the operation unit 10, FIG. 11(b) shows an example of the specific configuration of the input unit 12 shown in FIG. 11(a), and FIG. 11(c) shows an example of the specific configuration of the control unit 11 shown in FIG. 11(a).

As shown in FIG. 11(a), the operation unit 10 includes a stage movement control unit 13, an imaging control unit 14, a control unit 11, a display unit 16, an input unit 12, and a database unit 15.

The stage movement control unit 13 is configured to drive the drive source (motor) 120a of the drive unit 120 of the stage 110 based on a movement instruction signal.

The imaging control unit 14 is configured to drive a drive source (not shown) for moving the imaging unit 130 based on the imaging instruction signal and to cause the imaging unit 130 to image the cells.

The control unit 11 is configured to control the movement of the multiple stages by the drive unit 120, the movement of the imaging unit 130, and the imaging of the cell culture vessel 1 by the imaging unit 130, by transmitting a movement instruction signal to the stage control unit 13 and an imaging instruction signal to the imaging control unit 14 based on operations on the input unit 12.

Specifically, the control unit 11 has the function of recognizing which cell culture vessel 1 is placed in which vessel placement area of which stage 110 based on the read signal from the electromagnetic reader 140, and is configured to be able to control the movement of the stage 110 by the stage movement control unit 13, and further the movement and imaging operation of the imaging unit 130 by the imaging control unit 14, so that processing can be performed on the cell culture vessel 1 specified by the input unit 12 (moving it to a specified position within the device casing 100a and capturing an image of the bottom surface of the cell culture vessel 1).

The control unit 11 also includes a receiving unit that receives the input of the imaging schedule for the cells in the cell culture vessel 1 performed by the input unit 12.

The control unit 11 also controls the drive unit 120 so that the stage on which the cell culture vessel to be imaged is placed moves to an appropriate imaging position by outputting a movement instruction signal to the stage movement control unit 13 according to the imaging schedule described above, and controls the imaging unit 130 to move and capture an image of the bottom surface of the cell culture vessel 1 (i.e., the cells in the cell culture vessel 1) that has been moved to the appropriate imaging position by outputting an imaging instruction signal to the imaging control unit 14 according to this imaging schedule.

The display unit 16 is configured to display the display data from the control unit 11.

The input unit 12 is configured to allow the operator to input information through input operations, and the database unit 15 is configured to store the input information input from the input unit 12, the identification information (ID) read by the electromagnetic reader 140, and image data of the cells imaged by the imaging unit 130.

Here, the input unit 12 includes operation buttons for specifying various tasks in cell culture.

Specifically, as shown in FIG. 11(b), the input unit 12 has a container input button 12a for specifying the loading operation of placing the cell culture vessel 1 on the stage 110, a container unload button 12b for specifying the unloading operation of unloading the cell culture vessel 1 from the stage 110, an imaging schedule input button 12c for specifying the operation of inputting an imaging schedule, and an imaging button 12d for specifying the operation of imaging cells in a specified cell culture vessel 1. Information on the cell culture vessels stored in the device casing may be recorded, and if there is no space available in the device casing to load the cell culture vessel, the cell culture device may present that information to the operator or may be configured to reject the loading command.

In addition to the four operation buttons described above, the input section of the cell culture device 1001 according to the first modified example of the first embodiment (i.e., the cell culture device equipped with the culture medium exchange mechanism 1010) includes a culture medium supply button 12e for specifying the operation of supplying culture medium to a specified cell culture vessel 1, a culture medium discharge button 12f for specifying the operation of discharging culture medium from a specified cell culture vessel 1, and a culture medium exchange button 12g for specifying the operation of exchanging the culture medium in the specified cell culture vessel 1.

In addition, the memory section 11b included in the control section 11 stores a control program that enables the control section 11 to control the operation of each section (i.e., movement of the stage 110, movement of the imaging section 130, and imaging by the imaging section 130) required to perform the tasks specified by these operation buttons.

Therefore, when an operation to be performed on the cell culture vessel 1 is specified by operating any of these operation buttons 12a to 12d, the control unit 11 reads out from the memory unit 11b a control program corresponding to the operation specified by the operated button, and controls the stage movement control unit 13 and the imaging control unit 14. In the cell culture device 1001 of Modification 1 of Embodiment 1, the control unit 11 further controls the stage movement control unit 13 and the culture medium exchange mechanism 1010 by operating any of the operation buttons 12e to 12g so that the culture medium is supplied, discharged, or exchanged.

11(c), the control unit 11 has a processor unit 11a, a memory unit 11b, an input interface unit (input IF unit) 11c, an output interface unit (output IF unit) 11d, and an input/output interface unit (input/output IF unit) 11e, and operation signals from the input unit 12, imaging data (cell image data) obtained by the imaging unit 130, and read data obtained by reading the identification unit with the electromagnetic reader 140 are input to the processor unit 11a via the input IF unit 11c, control signals (including movement instruction signals and imaging instruction signals) from the processor unit 11a are output to the stage movement control unit 13 and the imaging control unit 14 via the output IF unit 11d, and imaging data from the imaging unit 130 is output from the processor unit 11a to the display unit 16 via the output IF unit 11d. Also, data access between the processor unit 11a and the database unit 15 is performed via the input/output IF unit 11e. The data accessed between the processor unit 11a and the database unit 15 includes imaging schedule information input from the input unit 12, image data of cultured cells captured by the imaging unit 130, and read data read by the electromagnetic reader 140.

In the cell culture equipment 100 of this embodiment, each cell culture vessel 1 has a vessel identification unit indicating a vessel ID that identifies the vessel, each stage 110 has a stage identification unit indicating a stage ID that identifies the stage 110, and each vessel mounting area of the stage has an area identification unit indicating an area ID that identifies the area, and these identification IDs are readable by the electromagnetic reader 140. Therefore, in the cell culture equipment 100, when a cell culture vessel 1 is carried into a predetermined stage, the stage into which the cell culture vessel 1 is carried moves to a position where the vessel ID, stage ID, and area ID can be read by the electromagnetic reader 140, and these identification IDs are read by the electromagnetic reader 140, and the control unit 11 uses these identification IDs to manage which cell culture vessel 1 is placed in which vessel mounting area of which stage 110. The container ID, stage ID, and area ID, i.e., information indicating which cell culture container 1 is placed in which container placement area of which stage 110, may be input to the control unit 11 by operating the input unit 12 when the operator carries the cell culture container 1 into the cell culture equipment 100.

However, in practice, ID management of stage positions in a cell culture device is generally performed in a memory associated with the operation record of the cell culture device (for example, a memory in which rotation angle information relative to a reference position is written in a memory area corresponding to each stage when the stage rotates). In this case, a stage ID is not required. Also, for the mounting area on each stage where the cell culture vessel is placed, a memory area corresponding to this mounting area is provided in the memory, and the ID (vessel ID) of the vessel placed in the corresponding mounting area is recorded in that memory area, so that there is no need to provide an area ID for each mounting area of the stage 110. The cell culture device of the present disclosure can manage the movement of the stage and the movement of the imaging unit, so that the positions of these members in the cell culture device can be similarly managed, and as a result, the cell culture device can hold position information of each mounting area in the memory. The cell culture device can identify the position of the cell culture vessel in the cell culture device by linking the position information of the stage and the imaging unit at the time of imaging with the vessel ID information obtained as a result of imaging.

Also, the container ID is necessary to track the location of the container since the container is moved to various locations other than the incubator.

The following describes the processing performed by the processor unit 11a in the control unit 11 when the operation buttons 12a to 12d in the input unit 12 are operated.

(Transportation of cell culture vessel 1)
When the container loading button 12a is operated on the input unit 12, the processor unit 11a in the control unit 11 reads out a container loading program, which is a control program, from the memory unit 11b, and outputs a control signal (movement instruction signal) to the stage movement control unit 13 according to the container loading program. As a result, the stage movement control unit 13 controls the drive unit 120 so that the stage 110 having one of the multiple (here, four) container mounting areas for mounting the cell culture container 1 among the multiple (here, three) stages 110 in the cell culture device 100, which is vacant, is positioned at the top in the device housing 100a. Note that, when there is a vacant container mounting area on the multiple stages 110, the stage 110 on which the cell culture container 1 is mounted and the container mounting area thereof may be selected so that the cell culture containers 1 are distributed as uniformly as possible in the cell culture device 100.

(Image capture of cultured cells in cell culture vessel 1)
When the imaging button 12d is operated on the input unit 12 to specify the identification ID (i.e., vessel ID) of the cell culture vessel 1 for which cells are to be imaged, the processor unit 11a in the control unit 11 reads out an imaging program, which is a control program, from the memory unit 11b and outputs a movement instruction signal to the stage movement control unit 13 in accordance with the imaging program. As a result, the stage movement control unit 13 controls the drive unit 120 so that the stage 110 on which the cell culture vessel 1 corresponding to the specified vessel ID is placed moves to the lowest position within the device housing 100a.

Furthermore, the control unit 11 controls the imaging control unit 14 by an imaging instruction signal according to the imaging program, thereby moving the imaging unit 130 horizontally to a position facing the container mounting area in which the cell culture container 1 specified by the container ID is placed, and causes the imaging unit 130 to image the cells. In this way, an image of the cells in the specified cell culture container 1 is captured.

(Imaging cultured cells according to an imaging schedule)
When the imaging schedule input button 12c is operated on the input section 12, the processor section 11a in the control section 11 reads out an imaging schedule input program, which is a control program, from the memory section 11b, and controls each section according to this program.

First, in the control unit 11, the processor unit 11a reads information (input screen information) indicating an input screen for an imaging schedule from the memory unit 11b, and transmits the input screen information to the display unit 16 via the output IF unit 11d. As a result, the input screen for an imaging schedule is displayed on the display unit 16.

The operator operates the input unit 12 to input the identification ID (vessel ID) of the cell culture vessel 1 to be imaged on the input screen displayed on the display unit 16, and further creates an imaging schedule by inputting the imaging date and time or imaging timing such as the imaging period and imaging cycle for each cell culture vessel 1 to be imaged. When imaging schedule information, which is input information created for each of the multiple cell culture vessels 1 to be imaged by this input unit 12, is supplied to the control unit 11, the processor unit 11a of the control unit 11 receives the imaging schedule information via the input IF unit 11c and stores it in the memory unit 11b. The imaging schedule information may also be stored in a database unit 15 external to the control unit 11.

When an imaging schedule for a specific cell culture vessel 1 is created in this manner, imaging according to the imaging schedule becomes possible. When the imaging button 12d is operated in this state, imaging of the cell culture vessel 1 is performed according to the imaging schedule.

That is, in the control unit 11, the processor unit 11a outputs a movement instruction signal to the stage movement control unit 13 according to the imaging schedule execution program read from the memory unit 11b. As a result, in the cell culture equipment 100, the stage movement control unit 13 controls the drive unit 120 so that the stage 110 on which the cell culture vessel 1 specified in the imaging schedule created by the operator is placed moves to the lowest position within the equipment housing 100a at the timing specified in the imaging schedule.

In addition, in the control unit 11, the processor unit 11a outputs an imaging instruction signal to the imaging control unit 14 according to the imaging schedule execution program. As a result, the imaging control unit 14 moves the imaging unit 130 to a position facing the container mounting area in which the cell culture container 1 specified in the imaging schedule is mounted, and causes the imaging unit 130 to image the cells. In this way, the cells in the cell culture container 1 are imaged according to the created imaging schedule. At this time, the control unit 11 may associate the imaging results with the container ID and store them in the database unit 15 as information indicating the culture state from moment to moment.

(Removal of cell culture vessel 1)
When the container unloading button 12b is operated on the input unit 12 and an identification ID (container ID) indicated by the container identification unit of the cell culture container 1 to be unloaded is specified, the processor unit 11a in the control unit 11 reads out a container unloading program, which is a control program, from the memory unit 11b and outputs a movement instruction signal to the stage movement control unit 13 in accordance with this container unloading program. As a result, the stage movement control unit 13 controls the drive unit 120 so that the stage 110 on which the cell culture container 1 corresponding to the specified container ID is placed is positioned at the top in the device housing 100a. In other words, the stage movement control unit 13 rotates the motor 120a in this manner.
Specifically, based on the read information (container ID and area ID) from the electromagnetic reader 140, the control unit 11 knows which cell culture container 1 is placed in which container placement area of which stage 110 in the cell culture equipment 100, and further, based on the identification ID (stage ID) of the stage 110 detected by the electromagnetic reader 140, it also knows in which rotational position each stage 110 in the cell culture equipment 100 is currently located.

Therefore, when the identification ID (container ID) of the cell culture container 1 to be removed is specified by the input unit 12, the control unit 11 controls the drive unit 120 under the control of the stage movement control unit 13 so that the stage 110 on which the cell culture container 1 corresponding to the specified container ID is placed moves to the top position within the device housing 100a.

As a result, the cell culture container 1 specified for removal is moved to a position where it can be removed from the device housing 100a.

The above are the operations that can be performed by operating the operation unit 10 of the cell culture device 100. However, the cell culture device 1001 according to variant 1 of embodiment 1 having the culture medium replacement mechanism 1010 further allows the following operations of adding culture medium to the cell culture vessel 1, discharging culture medium, and replacing culture medium.

(Supply of medium to cell culture vessel 1)
When the medium supply button 12e is operated on the input unit 12 and an identification ID (vessel ID) of the cell culture vessel 1 to which the medium is to be supplied is specified, the processor unit 11a in the control unit 11 reads out a medium supply program, which is a control program, from the memory unit 11b and outputs a movement instruction signal to the stage movement control unit 13 in accordance with the medium supply program. As a result, the stage movement control unit 13 controls the drive unit 120 so that the stage 110 on which the cell culture vessel 1 corresponding to the specified vessel ID is placed moves to the top position in the device housing 100a.

At this time, the control unit 11 also controls the movement mechanism (not shown) of the medium supply pipe 102a in accordance with the medium supply program to move the medium supply pipe 102a to above the designated cell culture vessel 1, and further controls the extension and contraction of the medium supply pipe 102a so that the tip of the medium supply pipe 102a reaches inside the designated cell culture vessel 1 located at the top, and further controls a medium supply source (not shown) so that the medium is supplied to the cell culture vessel 1. In this way, the medium is supplied to the designated cell culture vessel 1.

(Discharge of medium from cell culture vessel 1)
When the culture medium discharge button 12f is operated on the input unit 12 and the identification ID (container ID) of the cell culture container 1 from which the culture medium is to be discharged is specified, the processor unit 11a in the control unit 11 reads out a culture medium discharge program, which is a control program, from the memory unit 11b, and outputs a movement instruction signal to the stage movement control unit 13 in accordance with this culture medium discharge program, as in the case of culture medium supply. As a result, the stage movement control unit 13 controls the drive unit 120 so that the stage 110 on which the cell culture container 1 corresponding to the specified container ID is placed moves to the top position within the device housing 100a.

At this time, the control unit 11 also controls the movement mechanism (not shown) of the medium discharge pipe 102b in accordance with the culture medium discharge program to move the medium discharge pipe 102b above the designated cell culture vessel 1, and further controls the extension and contraction of the medium discharge pipe 102b so that the tip of the medium discharge pipe 102b reaches the medium in the designated cell culture vessel 1 located at the top, and controls the medium suction source (not shown) so that the medium is discharged from the cell culture vessel 1. This causes the medium to be discharged from the designated cell culture vessel 1.

(Culture medium replacement in cell culture vessel 1)
When the medium exchange button 12g is operated on the input unit 12 and the identification ID (vessel ID) of the cell culture vessel 1 for which the medium is to be exchanged is specified, the processor unit 11a in the control unit 11 reads out a medium exchange program, which is a control program, from the memory unit 11b, and outputs a movement instruction signal to the stage movement control unit 13 in accordance with the medium exchange program, similar to the case of medium supply or medium discharge. As a result, the stage movement control unit 13 controls the drive unit 120 so that the stage 110 on which the cell culture vessel 1 corresponding to the specified vessel ID is placed moves to the top position in the device housing 100a.

At this time, the control unit 11, in accordance with the culture medium replacement program, discharges the culture medium from the culture medium discharge pipe 102b in the designated cell culture vessel 1, similar to the culture medium discharge operation described above, and then supplies the culture medium from the culture medium supply pipe 102a in the designated cell culture vessel 1, similar to the culture medium supply operation described above. As a result, the culture medium is supplied to the designated cell culture vessel 1, and the culture medium is replaced.

Next, a method of using the cell culture device 100 will be described together with its operation.
Figure 12 is an oblique view for explaining the operation of the cell culture equipment 100 shown in Figure 3(a), and shows the stage 110 that is closest to the imaging unit 130 among the four stages 110 in the cell culture equipment 100 shown in Figure 3(a) and the three cell culture containers 1a to 1c placed on it.

Here, we will explain the case of photographing cells in the rightmost cell culture vessel 1c placed on one of the four stages (first stage 110a) provided on the cell culture device 100.

In this case, the operator operates the image capture button 12d (see FIG. 11(b)) on the input unit 12 shown in FIG. 11(a) and, of the three cell culture vessels 1a-1c mounted on the first stage 110a, specifies the cell culture vessel 1c (represented as a dot) at the right end (the one closest to the driving rotor 121a) as the cell culture vessel 1 to be imaged by inputting its vessel ID. When such an input operation is performed on the input unit 12, the input unit 12 outputs operation information to the control unit 11. In the control unit 11, as shown in FIG. 11(c), the operation information from the input unit 12 (including the identification ID of the cell culture vessel 1 to be imaged) is input to the processor unit 11a via the input IF unit 11c.

The memory unit 11b of the control unit 11 currently stores placement information indicating which identification ID of the cell culture vessel 1 is placed in which vessel mounting area of which stage 110, and the processor unit 11a determines in which vessel mounting area of which stage 110 the cell culture vessel 1c to be imaged is placed based on this placement information.

For example, if the processor unit 11a detects as a result of this determination that the cell culture vessel 1c (represented by a dot) to be imaged is currently located at the right edge of the paper (the edge on the driving rotor 121a side) of the stage 110a, which is located at the highest point, as shown in FIG. 3(a), the processor unit 11a controls the stage movement control unit 13 in accordance with the imaging program read from the memory unit 11b to drive the motor 120a of the drive unit 120, thereby moving the first stage 110a to the lowest point, as shown in FIG. 12.

In addition, when the default position of the imaging unit 130 is a position for imaging the cell culture vessel 1 at the left end of the stage 110a, the processor unit 11a controls the imaging control unit 14 according to the imaging program to drive the driving source (not shown) of the imaging unit 130, thereby moving the imaging unit 130 from the left side of the stage 110 to a position facing the cell culture vessel 1c at the right end.

Once the positional relationship between the imaging unit 130 and the cell culture vessel 1c to be imaged has been adjusted in this manner, the imaging control unit 14 is controlled to cause the imaging unit 130 to perform an operation of imaging the cells in the cell culture vessel 1c to be imaged.

When the imaging data (image data) captured by the imaging unit 130 in this manner is transmitted from the imaging unit 130 to the control unit 11, the processor unit 11a in the control unit 11 receives the imaging data via the input IF unit 11c, and stores the received imaging data in the database unit 15 via the input/output IF unit 11e. As a result, in the cell culture equipment 100, image data of the cells in the cell culture vessel 1 specified by the operator is accumulated in the database unit 15 as the observation results of the cell culture.

In addition, if an imaging schedule is input and images of multiple cell culture vessels 1 are to be captured in accordance with the imaging schedule, the imaging schedule can be input from the input unit 12 to the control unit (MPU) 11 of the operation unit 10 before starting the culture.

In this case, the control unit 11 can control the stage movement control unit 13 and the imaging control unit 14 so that the cells in all cell culture containers 1 listed in the imaging schedule are imaged at the imaging timing determined in the imaging schedule.

In other words, the control unit 11 controls the stage movement control unit 13 to rotate and move the stage 110 so that the cells in each cell culture vessel 1 are imaged at an appropriate imaging position relative to the imaging unit 130 according to the imaging schedule, and controls the imaging control unit 14 to move the imaging unit 130 horizontally to the specified cell culture vessel 1, causing the imaging unit 130 to perform an imaging operation for the specified cell culture vessel 1.

In this way, the imaging data of the cells in each cell culture vessel 1 captured according to the imaging schedule is compiled in chronological order for each cell culture vessel 1 by the processor unit 11a and stored in the database unit 15 as the observation results of the cultured cells in each cell culture vessel 1.

In the cell culture device 100 of this embodiment configured as described above, the stage 110 on which the cell culture vessel 1 is placed is moved vertically, and when the stage 110 is positioned at an appropriate position (e.g., the lowest point), the imaging unit 130 located on the bottom surface of the cell culture device 100 images the cells in the cell culture vessel 1 placed on this stage 110, so that cell culture and its progress can be observed efficiently within a specified space.

In the first modification of the first embodiment, the cell culture device 1001 is shown as a device that changes the culture medium in response to an operator's operation, but the cell culture device of the present invention may also change the culture medium automatically in response to the culture conditions, such as the shape of the cultured cells and the color of the culture medium.

Therefore, as the second embodiment below, we will explain a system that automatically changes the culture medium, that is, a system that detects the culture state (cell shape, culture medium color, etc.) in each cell culture device and feedback-controls the culture state, such as changing the culture medium and culture conditions, according to the detected culture state.

(Embodiment 2)
Figure 13 is a diagram showing an example of the configuration of an operation unit 20 included in a cell culture device according to this embodiment 2, Figure 13(a) is a block diagram showing the configuration of the operation unit 20 of embodiment 2, Figure 13(b) shows an example of a specific configuration of the input unit 22 shown in Figure 13(a), and Figure 13(c) shows an example of a specific configuration of the control unit 21 shown in Figure 13(a).

The cell culture device of embodiment 2 includes the configuration of the cell culture device 100 of embodiment 1, as well as a culture medium exchange mechanism 1010 (see Figures 7 and 8) similar to the cell culture device 1001 of modified example 1 of embodiment 1.

In addition, in this embodiment 2, instead of the RF tag that is the identification unit (vessel IDD) of the cell culture vessel 1 in embodiment 1, an ID tag that identifies the cell culture vessel 1 by character notation is attached, and an OCR reader 240 is attached to the imaging unit 130 instead of the electromagnetic reader 140 in embodiment 1. Here, the OCR reader 240 is an image sensor with an OCR function, which reads the character notation portion of the ID tag contained in the image of the bottom surface of the cell culture vessel 1 as image information, extracts the text information of the character notation, and outputs the image information of the bottom surface of the cell culture vessel 1.

The operation unit 20 of the cell culture device of embodiment 2 includes a stage movement control unit 13, an imaging control unit 14, a control unit 21, a display unit 16, an input unit 22, and a database unit 15. The configuration other than the control unit 21 and the input unit 22 is the same as that of the operation unit 10 of embodiment 1 shown in FIG. 11(a). The control unit 21 and the input unit 22 will be described in detail below.

(Control unit 21)
In addition to the functions of the control unit 11 in embodiment 1, the control unit 21 has a function of analyzing text information from the OCR reader 240 to identify individual cell culture vessels 1, and analyzing image information from the OCR reader 240 to detect the culture status such as the shape of the cells in the cell culture vessel 1 and the color of the culture medium, and storing the culture status information in the memory unit 21b in association with the identification ID (vessel ID) of each cell culture vessel 1.

Furthermore, this control unit 21 determines whether or not it is necessary to replace the culture medium or adjust the culture conditions based on the detection results of the culture status, and controls the stage movement control unit 13 and the culture medium replacement mechanism 1010 (see Figures 7 and 8) so that the culture medium is replaced in the cell culture vessel 1 as necessary according to the determination result, and is also configured to instruct the incubator (not shown) to change the culture conditions.

In addition, a schedule for changing the culture medium (culture medium exchange schedule) can be set for the control unit 21. When a culture medium exchange schedule is set, the control unit 21 basically performs the culture medium exchange in each cell culture vessel 1 according to the culture medium exchange schedule, and controls the stage movement control unit 13 and the culture medium exchange mechanism 1010 so that the culture medium is exchanged at a timing other than the timing indicated in the culture medium exchange schedule only when it is determined that the culture medium needs to be exchanged in a specific cell culture vessel 1 based on the identification ID (vessel ID) information and the culture status information obtained by the OCR reader 240.

(Input unit 22)
The input section 22 included in the operation section 20 constituting the cell culture equipment of this embodiment 2 has the same configuration as the input section 12 included in the operation section 10 of the cell culture equipment 100 of embodiment 1, and further has a culture medium exchange schedule input button 22e and an automatic culture medium exchange button 22f.

Therefore, when buttons 12a to 12d are operated on input unit 22, control unit 21 performs the same processing as control unit 11.

When the medium exchange schedule input button 22e and the automatic medium exchange button 22f are operated on the input unit 22, the processor unit 21a in the control unit 21 reads out the medium exchange schedule execution program from the memory unit 21b and controls each unit according to this program.

(Enter medium exchange schedule)
First, when the culture medium exchange schedule input button 22e is operated, the processor unit 21a of the control unit 21 reads information (input screen information) showing an input screen for the culture medium exchange schedule from the memory unit 21b based on the culture medium exchange schedule input program read from the memory unit 21b, and transmits the input screen information via the output IF unit 11d to the display unit 16. As a result, the input screen for the culture medium exchange schedule is displayed on the display unit 16.

The operator operates the input unit 22 to input the identification ID (container ID) of the cell culture vessel 1 to be subjected to medium exchange into the input screen displayed on the display unit 16, and further creates a medium exchange schedule by inputting the date and time, or the timing of medium exchange such as the period and cycle for each cell culture vessel 1 to be subjected to medium exchange.

When the medium exchange schedule information, which is input information created by the input unit 22 for each of the multiple cell culture vessels 1 targeted for medium exchange, is supplied to the control unit 21, the processor unit 21a in the control unit 21 receives the medium exchange schedule information via the input IF unit 11c and stores it in the memory unit 21b. The medium exchange schedule information may also be stored in the database unit 15 outside the control unit 21.

When the culture medium exchange schedule for all cell culture vessels 1 in the cell culture equipment 200 is created in this manner, the processor unit 21a in the control unit 21 outputs a movement instruction signal to the stage movement control unit 13 according to the culture medium exchange schedule execution program. As a result, in the cell culture equipment 200, the stage movement control unit 13 controls the drive unit 120 so that the stage 110 on which the cell culture vessel 1 specified in the culture medium exchange schedule created by the operator is placed is moved to the top position within the equipment housing 100a at the timing indicated in the culture medium exchange schedule.

Furthermore, in the control unit 21, the processor unit 21a controls the stage movement control unit 13 and the culture medium exchange mechanism 1010 according to the culture medium exchange schedule execution program. As a result, in the cell culture equipment 200, the culture medium exchange mechanism 1010 exchanges the culture medium in the cell culture vessel 1 specified in the culture medium exchange schedule.

(Automatic medium exchange)
Furthermore, when the automatic culture medium exchange button 22f is operated on the input unit 22, the processor unit 21a of the control unit 21 reads out an automatic culture medium exchange program from the memory unit 21b, and controls the stage movement control unit 13 and the OCR reader 240 according to the automatic culture medium exchange program. As a result, the stage movement control unit 13 controls the drive unit 120 so that each stage 110 passes through the lowest position in the equipment housing 100a at a constant cycle, and controls the OCR reader 240 so that the OCR reader 240 detects an image including characters written on an ID tag on the bottom surface of the cell culture vessel 1 placed on each stage 110 when each stage 110 passes through the lowest position in the equipment housing 100a.

At this time, the control unit 21 analyzes the text notation of the ID tag using an OCR function, recognizes it as text information (vessel ID), and associates the recognized information (vessel ID) with an image of the bottom surface of the cell culture vessel 1, and stores this information together with the date and time of acquisition in the memory unit 21b or database unit 15. This process is repeated for all cell culture vessels 1, and the state of the medium and culture is recorded in the memory unit 21b or database unit 15.

The control unit 21 further controls the culture medium exchange mechanism 1010 and the stage movement control unit 13 so that the culture medium is exchanged according to the stored culture medium and culture state in each cell culture vessel 1, and at the same time controls the incubator (not shown) to adjust the culture conditions.

Next, an example of the operation of the cell culture device 200 of the second embodiment will be described.
In the cell culture equipment 200 of embodiment 2 having such a configuration, when the container load button 12a, the container unload button 12b, the shooting schedule input button 12c, or the shooting button 12d is operated, the control unit 21 performs control similar to that performed by the control unit 11 in the cell culture equipment 100 of embodiment 1.

In addition, in the cell culture device 200 of embodiment 2, when the culture medium exchange schedule input button 22e is operated on the input unit 22, the processor unit 21a in the control unit 21 reads out a culture medium exchange schedule input program from the memory unit 21b and controls each unit according to this program.

Specifically, the processor unit 21a reads out the input screen for the culture medium exchange schedule from the memory unit 21b and displays it on the display unit 16.

When the operator inputs the necessary information, such as the identification ID of the cell culture vessel 1 to be subjected to medium replacement and the timing of the medium replacement, into the input screen displayed on the display unit 16, the control unit 21 creates a medium replacement schedule and stores it in the memory unit 21b.
Thereafter, when the automatic culture medium exchange button 22f is operated on the input unit 22, in the control unit 21, the processor unit 21a reads out an automatic culture medium exchange program from the memory unit 21b, and the processor 21a controls the stage movement control unit 13, the culture medium exchange mechanism 1010, and the incubator (not shown) so that culture medium exchange and adjustment of culture conditions are performed in accordance with this program.

Specifically, the control unit 21 controls the stage movement control unit 13 and the culture medium exchange mechanism 1010 so that culture medium exchange in each piece of cell culture equipment is performed at a timing based on the culture medium exchange schedule, and also controls the stage movement control unit 13 and the culture medium exchange mechanism 1010 so that culture medium exchange is performed at a timing according to the culture status obtained from the text information (container ID) and image information (culture status such as the shape of the cultured cells and the color of the culture medium) obtained by the OCR reader 240, and at the same time controls the incubator (not shown) so that the culture conditions are adjusted.

This makes it possible to automatically complete cell culture in all cell culture containers 1 housed in the cell culture device 200.

In the above-mentioned embodiment 1 and its variations 1 to 3 as well as embodiment 2, various processes such as moving the stage and the imaging unit, photographing the cell culture vessel, and changing the culture medium are performed in the cell culture equipment by operating buttons on the input unit of the operation unit mounted on the cell culture equipment. However, operation information may be sent to the cell culture equipment from outside the equipment, that is, from an information processing device such as a personal computer or smartphone equipped with a dedicated application, via a communication line including the Internet.

In addition, the imaging data (image information) of the cell culture vessel acquired by the cell culture device can be stored not only in a database unit installed in the cell culture device, but also transferred to and stored in a database unit external to the cell culture device.

In particular, information regarding cell culture obtained from multiple cell culture devices sold may be collected and managed in a central server that manages each cell culture device.

In addition, when multiple cell culture devices are managed by a central server, information such as imaging schedules and culture medium replacement schedules for each cell culture device may be stored in the memory or database section of the corresponding cell culture device, or the central server may collectively manage information such as imaging schedules and culture medium replacement schedules for each of the managed cell culture devices.

In the above-mentioned embodiment 1 and its variations 1 to 3, as well as embodiment 2, the structure of the stage 110 is shown as a structure in which the container mounting table 1101 is connected to the driving rotor 121a and the driven rotor 121b by the support shaft portion 1102, but the structure of the stage 110 is not limited to this, and the container mounting table 311 may be suspended from a support 312 stretched between the driving rotor 121a and the driven rotor 121b (see FIG. 14). Below, a cell culture device 300 having a stage 310 with such a structure will be described.

(Embodiment 3)
14A and 14B are diagrams showing a cell culture device 200 according to a third embodiment of the present invention, where FIG. 14A shows the internal structure thereof and FIG. 14B shows an enlarged view of a stage 310 in FIG. 14A.

The cell culture device 300 of this embodiment 3 has a stage 310 and a cell culture container 3 that have a different structure from the cell culture device 100 of embodiment 1 shown in FIG. 4(a).

In other words, as shown in FIG. 14(b), the stage 310 (310a to 310d) of the cell culture equipment 300 has a container mounting table 311 on which the cell culture container 3 is placed, a rod-shaped support 312 that supports the container mounting table 311, and a connecting piece 313 that connects the container mounting table 311 to the support 312, and the container mounting table 311 is configured to be able to mount five cell culture containers 3. In this stage 310, one end of the support 312 is connected to the driving rotor 121a, and the other end of the support 312 is connected to the driven rotor 121b, so that the driving rotor 121a and the driven rotor 121b of the drive unit 120 that drives the stage 310 are connected by the support 312.

The upper end of the connecting piece 313 is rotatably attached to the support 312. Therefore, even if the support 312 rotates due to the rotation of the drive ring body 121a, the container mounting table 311 is always suspended below the support 312 by the connecting piece 313 due to the action of gravity.

Furthermore, in the cell culture device 300 of this embodiment 3, a bottle-shaped container 3 including a container body 3a and a cap 3b is used as the cell culture container instead of the cell culture container (petri dish) 1 of embodiment 1 shown in FIG. 3.

The rest of the configuration is the same as the cell culture device 100 shown in embodiment 1.

Like the cell culture device 100 of the first embodiment, the cell culture device 300 of the third embodiment also makes it possible to efficiently culture cells and observe their progress within a given space.
In the above-mentioned first to third embodiments, as shown in Fig. 3(a), the mechanism for supporting the stage includes a rotor 121a rotatably supported on one of the opposing side walls of the device housing 100a of the cell culture device 100 and a rotor 121b rotatably supported on the other opposing side wall, and one end of the stage 110 is rotatably supported by the driving rotor 121a and the other end of the stage 110 is rotatably supported by the driven rotor 121b, but the mechanism for supporting the stage is not limited to one including a rotor, and may be, for example, a ring-shaped chain meshed with a plurality of sprockets that supports the stage, or a plurality of shelves included in a rack that supports the stage. The following describes these mechanisms for supporting the stage in detail.

FIG. 15 is a schematic diagram showing a member other than a rotor that supports the stage, and shows the mechanism for supporting the stage as viewed from a cross section corresponding to the cross section along line Y-Y in FIG. 3(a). In particular, FIG. 15(a) shows a case in which the mechanism for supporting the stage includes a circular chain that meshes with three sprockets, and FIG. 15(b) shows a case in which the mechanism for supporting the stage includes a rack with at least two shelves of different heights on which the stage is placed.

(Stage support mechanism using a circular chain)
First, a specific structure in which a circular chain meshing with a sprocket is used to support the stage will be described with reference to FIG.

In the mechanism shown in FIG. 15(a), three sprockets 1202a to 1202c are rotatably attached to one side wall of the device housing 100a, two of which, sprockets 1202a and 1202b, are arranged horizontally facing each other near the upper end of the side wall, and the remaining sprocket, 1202c, is arranged at the bottom of the side wall close to the imaging unit 130.

A circular chain 1201 is stretched across these three sprockets 1202a to 1202c so as to mesh with each of the sprockets. Three similar sprockets (not shown) are attached to the other side wall of the device housing 100a, and a circular chain (not shown) is stretched across these sprockets.

Then, the stage is attached between the circular chain 1201 on one side wall and the circular chain (not shown) on the other side wall so that its mounting surface always faces vertically, thereby realizing a configuration in which the stage is supported by a pair of chains. In this case, at least one of the three sprockets becomes a drive sprocket that drives the circular chain.

Next, a specific structure for supporting the stage using a rack with at least two shelves will be explained using Figure 15(b).

(Stage support mechanism using rack)
15(b), a rack 1203 having four shelves 1203a to 1203d arranged vertically is provided along one side wall within the device housing 100a, and a lifting device 1204 for raising and lowering the stage 110 is provided on the other side wall. This lifting device 1204 has a lifting arm 1204a that holds the stage 110, and an arm driver 1204b that raises and lowers the lifting arm 1204b.

In this mechanism, the lifting device 1204 allows the stage 110 to be moved in and out of each shelf of the rack, thereby realizing a configuration in which the stage 110 is supported by shelves 1203a to 1203d of the rack 1203.

When using a rack 1203, a robot arm for moving the stage 110 may be provided instead of the lifting device 1204 for moving the stage 110 between the shelf of the rack and the imaging position.

As described above, the present invention has been illustrated using a preferred embodiment of the present invention, but the present invention should not be interpreted as being limited to this embodiment. It is understood that the scope of the present invention should be interpreted only by the claims. It is understood that a person skilled in the art can implement an equivalent scope based on the description of the specific preferred embodiments of the present invention and common technical knowledge from the description of the present invention. It is understood that the contents of the documents cited in this specification should be incorporated by reference into this specification in the same manner as if the contents themselves were specifically described in this specification.

The present invention is useful for providing a cell culture device that can efficiently perform cell culture within a given space and monitor the progress of cultured cells by imaging.

1, 3 Cell culture vessel (petri dish)
1a, 3a Petri dish body 1b Petri dish lid 3b Cap 10, 20 Operation unit 11, 21 Control unit (MPU)
11a, 21a Processor section 11b, 21b Memory section 11c Input IF section 11d Output IF section 11e Input/output IF section 12, 22 Input section 12a Container loading button 12b Container unloading button 12c Shooting schedule input button 12d Shooting button 12e Culture medium addition button 12f Culture medium discharge button 12g Culture medium replacement button 13 Stage movement control section 14 Imaging control section 15 Database section 16 Display section 22e Culture medium replacement schedule input button 22f Automatic culture medium replacement button 100, 200, 1001, 1002 Cell culture device 100a, 100b Device housing (housing)
REFERENCE SIGNS LIST 101 Top opening 101a Top lid 102a Culture medium supply pipe 102b Culture medium discharge pipe 103 Lid opening/closing member 103a Adsorption part 103b Support rod 110 Stage 110a, 210a First stage 110b, 210b Second stage 110c, 210c Third stage 110d, 210d Fourth stage 111, 211 Container placement table 120 Drive part 120a Drive source 120a1 Rotating shaft body 120b Reduction gear 121a Drive rotor 121b Driven rotor 122 Sun gear 123 Planetary gear 123a Connecting member 124 Internal gear 125 Support roller 126 Central shaft 130 Imaging part 140 Electromagnetic reader 212 Support 213 Connection piece 240 OCR reader 1010 Culture medium exchange mechanism 1010a Guide member 1011 First guide groove 1012 Second guide groove 1013 Third guide groove 1101 Container placement stand 1101a Opening 1102 Support shaft portion L Culture medium

Claims (16)

a plurality of stages for mounting cell culture vessels;
A drive unit that moves the stage in a direction including a vertical direction;
and a movable imaging unit configured to image cells in a cell culture vessel placed on the stage. The cell culture device according to claim 1, wherein the imaging unit is configured to image the cells in the cell culture vessel from below. The cell culture device according to claim 2, wherein the imaging unit is movable in the horizontal direction. The cell culture device according to claim 1, wherein each of the plurality of stages is configured to accommodate a plurality of the cell culture vessels. The cell culture device according to claim 4, wherein at least one of the stages has a horizontal size of about 25 cm to about 35 cm in the long side direction and about 10 cm to about 20 cm in the short side direction. The cell culture device according to claim 1, wherein the imaging unit includes a cell observation device. The cell culture device according to claim 1, further comprising a control unit that controls the movement of the stages by the drive unit and the movement of the imaging unit. The cell culture device according to claim 7, further comprising a reader for reading the identification unit attached to the cell culture vessel. The cell culture device according to claim 8, wherein the control unit includes a receiving unit that receives an input of an imaging schedule for the cells in the cell culture vessel. The cell culture device according to claim 9, wherein the control unit controls the drive unit to move the stage on which the cell culture vessel that is the subject of the imaging schedule is placed to an imaging position according to the imaging schedule, and controls the imaging unit to move and capture images of the cells in the cell culture vessel that has been moved to the imaging position. The cell culture device according to claim 1, configured to be installed in an incubator. The cell culture device according to claim 1, wherein the drive unit is a rotating body. a housing that accommodates the stage, the drive unit, and the imaging unit;
The cell culture device according to claim 1 , further comprising: a mechanism for controlling a cell culture environment within the housing. The cell culture device according to claim 13, wherein at least one of the top, back and side of the housing can be opened and closed, and the medium for cell culture can be replaced from at least one of the top, back and side. The cell culture device according to claim 1, configured to operate the drive unit for temperature equalization between the cell culture vessels according to a schedule created based on the operation of the drive unit for imaging or operations on the cell culture vessels or the schedule for the operation of the drive unit. Placing a cell culture vessel containing cells on the stage of the cell culture device according to any one of claims 1 to 15;
Culturing the cells; and
and capturing an image of the cells using the imaging unit.

Images