JP2020130133A - Imaging system - Google Patents

Abstract

To suppress a space being an object of atmosphere control to a small volume and properly control atmosphere in transport between a storage position and an imaging position.SOLUTION: An imaging system of the invention comprises: an imaging part 3 for imaging a sample carried to a sample container; a storage part 2 for storing a culture chamber which has a storage chamber capable of storing a sample container; a transport part 4 for transporting the culture chamber storing the sample container; and a control part 5 for controlling atmosphere in the storage chamber. On the storage part, a holding body for storage for holding the culture chamber and a transport holding body for holding the culture chamber when transporting the culture chamber by the transport part have respectively, a connector to be connected to the storage space of the culture chamber, and by engagement to connectors C1, C2 on the culture chamber side, atmosphere control of the storage space is selectively executed.SELECTED DRAWING: Figure 12

Description

The present invention relates to a technique for imaging a sample stored in an atmosphere-controlled environment, for example, a sample such as cells cultured in a predetermined culture environment, as an imaging object.

In the technical fields of medicine and biochemistry, observation of cells and microorganisms cultured in a container is performed. As a method of observing cells or the like to be observed without affecting them, a technique of imaging cells or the like using a microscope or the like has been proposed. The sample is cultured in an environment in which conditions such as temperature, humidity, and atmosphere composition are kept constant by using, for example, an incubator device. At the time of imaging, the sample is taken out from such a culture environment and used in the imaging device. Set.

In this type of imaging, for example, in order to observe changes in the sample over time, multiple imaging may be performed at intervals while continuing the culture. In such a case, the sample may be altered or the state of the cells may be changed due to a change in the culture environment of the sample, even temporarily.

As a solution to this problem, for example, there is a technique described in Patent Document 1. In this prior art incubator device, the internal space of the incubator capable of accommodating a plurality of sample containers partially protrudes outward, and the sample container placed on this portion is imaged by an external imaging device. This ensures that the sample is not exposed to external space during culture and imaging. The transport robot installed in the incubator is responsible for transporting the sample container in the incubator.

JP-A-2009-136233

In the above-mentioned conventional technology, the internal volume of the incubator is reduced by adopting an articulated arm as the transfer robot and devising the movement during transfer, but a large space for accommodating a plurality of sample containers and the transfer robot is provided. I still need it. This not only leads to an increase in the size of the device, but also increases the volume of the space for controlling the atmosphere, which makes appropriate atmosphere control difficult.

Therefore, there is a technology that can create an appropriate culture environment by controlling the atmosphere of a small volume space, and can maintain the culture environment even during transportation between the storage place and the place for imaging. Desired. However, a technology capable of meeting such a demand has not been established so far.

The present invention has been made in view of the above problems, and is a technique capable of appropriately controlling the atmosphere even during transportation between the storage location and the imaging location while suppressing the space subject to atmosphere control to a small volume. The purpose is to provide.

One aspect of the present invention includes an imaging unit that captures an image of a sample carried in a sample container, a storage unit that stores a culture chamber having a storage chamber capable of accommodating the sample container, and the storage unit and the imaging unit. It is an imaging system including a transport unit for transporting the culture chamber in which the sample container is housed and a control unit for controlling the atmosphere in the containment space. In this imaging system, in order to achieve the above object, the storage unit has a storage holder for detachably holding the culture chamber, and the transport unit holds the culture chamber when transporting the culture chamber. Each of the storage retainer and the transport retainer has a connector that is connected to the accommodation space when holding the culture chamber, and the control unit has the control unit. The atmosphere is controlled for the culture chamber held in the storage holder via the connector of the storage holder, and the culture chamber held in the transport holder is transported. The atmosphere is controlled via the connector of the holding body.

In the invention configured as described above, when the culture chamber is stored in the storage unit, the control unit controls the atmosphere in the storage space via the connector provided on the storage holder. On the other hand, when the culture chamber is held by the transfer unit, the control unit controls the atmosphere in the accommodation space via the connector provided on the transfer holder. Therefore, the atmosphere control from the control unit for the accommodation space can function regardless of whether the culture chamber is stored in the storage unit or held by the transport unit.

Further, the sample container is transported from the storage unit to the imaging unit in a state of being housed in the culture chamber in which the atmosphere of the storage space is controlled. Therefore, it is sufficient that the storage space in the culture chamber in which the control unit should control the atmosphere has a volume that can accommodate the sample container inside.

As described above, according to the present invention, the atmosphere control from the control unit to the culture chamber functions in both the state of being stored in the storage unit and the state of being transported by the transport unit. In addition, the storage space in the culture chamber where the control unit should control the atmosphere can be small in volume. Therefore, it is possible to appropriately control the atmosphere even during transportation between the storage location and the imaging location while suppressing the space subject to atmosphere control to a small volume.

It is a figure which shows the schematic structure of one Embodiment of the image pickup system which concerns on this invention. It is a flowchart which shows the outline of the operation of this image pickup system. It is a figure which shows the movement of the transport part at the time of transporting a culture chamber. It is a figure which shows the movement of the transport part at the time of transporting a culture chamber. It is a figure which shows the movement of the transport part at the time of transporting a culture chamber. It is an exploded view which shows the structure of a culture chamber. It is a figure which shows the relationship of the connector between a culture chamber and a support base. It is sectional drawing which shows the state of engagement of the air supply connector. It is a figure which shows the relationship of the connector between a culture chamber and a support hand. It is a figure which shows the state of delivery of a culture chamber from a support base to a support hand. It is a figure which shows the state of delivery of a culture chamber from a support base to a support hand. It is a block diagram which shows the control system of this image pickup system. It is a figure which illustrates other structure of a culture chamber.

Hereinafter, specific embodiments of the imaging system according to the present invention will be described. The present embodiment is an imaging system that images a sample such as a fertilized human egg, such as cells continuously cultured in an incubator, by an appropriate imaging method. This imaging system 100 is suitable for so-called time-lapse imaging in which a sample cultured in a constant culture environment is imaged at predetermined time intervals. The imaging method is not particularly limited, but for example, an imaging method based on optical coherence tomography (OCT) technology can be preferably applied.

FIG. 1 is a diagram (front view and plan view) showing a schematic configuration of an embodiment of an imaging system according to the present invention. The imaging system 100 has a structure in which a storage unit 2, an imaging unit 3, and a transport unit 4 are arranged on a base 101. Further, the imaging system 100 includes a control unit 5 described later. In order to show the directions in each of the following figures in a unified manner, the XYZ orthogonal coordinate axes are set as shown in FIG. Here, the XY plane represents the horizontal plane. Further, the Z axis represents the vertical axis, and more specifically, the (−Z) direction represents the vertical downward direction.

The storage unit 2 has a function of storing a portable culture chamber 9 in which the atmosphere of the internal space is adjusted to a predetermined culture environment. Specifically, the storage unit 2 includes a support column 21 whose vertical direction is the longitudinal direction and whose lower end is fixed to the base 11, and a flat plate-shaped support base 22 which is attached to the support column 21 and whose upper surface is a flat support surface. It has. The support base 22 supports the culture chamber 9 from below by contacting the central portion of the lower surface of the culture chamber 9. When a plurality of support bases 22 are provided, they are arranged on the (−Y) direction side surface of the support column 21 at a constant pitch in the vertical direction (Z direction). In this embodiment, five support bases 22 are provided, and each support base 22 can support the culture chamber 9 one by one. The structure of the culture chamber 9 will be described later.

The imaging unit 3 has a function of imaging a sample housed inside the culture chamber 9. The configuration is not particularly limited, but as shown in FIG. 1, for example, it is assumed that one or a plurality of objective lenses 32 that can be used properly according to the purpose are attached to the upper part of the main body 31 containing a camera, an illumination light source, or the like. be able to. Further, although the detailed reason will be described later, a structure such as a camera or an illumination optical system may be provided in the upper space shown by the alternate long and short dash line in FIG.

The transport unit 4 has a function of transporting the culture chamber 9 between the storage unit 2 and the imaging unit 3. Specifically, the transport unit 4 takes out one of the culture chambers 9 stored in the storage unit 2, transports it to the imaging unit 3, and returns the culture chamber 9 after imaging by the imaging unit 3 to the storage unit 2. .. In order to realize this function, the transport unit 4 has the following structure.

That is, the transport portion 4 has a base portion 41 attached to the upper surface of the base material 11 so as to be horizontally movable with respect to the guide rail 12 extending in the Y direction. A support column 42 extending upward from the upper surface of the base portion 41 is provided. Guide rails 43, 43 extending in the vertical direction are attached to the side surface of the support column 42 on the (+ X) direction side. A slider 44 is attached to the guide rail 43 so as to be able to move up and down. A support hand 45 extending in the (+ X) direction and having a flat upper surface is attached to the slider 44. As will be described in detail later, the support hand 45 is a flat plate-shaped member having a large notch 451 in the central portion, and supports the culture chamber 9 by bringing its upper surface into contact with the lower peripheral edge of the culture chamber 9. It is possible.

As will be described later, the control unit 5 controls the horizontal movement of the base portion 41 along the guide rail 12 and the vertical movement of the slider 44 along the guide rail 43. By combining the horizontal movement of the base portion 41 and the ascending / descending movement of the slider 44, the culture chamber 9 is transported from one of the support bases 22 of the storage unit 2 to the image pickup unit 3 or from the image pickup unit 3 to the original support base 22. Is realized.

As described above, in the imaging system 100, the culture chamber 9 containing the sample to be imaged is stored in the storage unit 2. The culture chamber 9 is transported to the imaging unit by the transport unit 4 as needed, and is subjected to imaging by the imaging unit 3. Further, the culture chamber 9 after imaging is returned to the storage unit 2. The main feature of the imaging system 100 is the inside of the culture chamber 9 throughout the period in which the culture chamber 9 is stored in the storage unit 2, the period in which the culture chamber 9 is transported by the transport unit 4, and the period in which the image is taken by the image pickup unit 3. The atmosphere control of the space is functioning, which maintains a suitable culture environment for the sample. Hereinafter, the configuration of the present embodiment that enables this will be described in more detail.

FIG. 2 is a flowchart showing an outline of the operation of this imaging system. First, the culture chamber 9 containing the sample to be imaged is carried into the imaging system 100 and placed on the support 22 of the storage unit 2. As described above, the atmosphere control in the culture chamber 9 functions even when it is placed on the support base 22 (step S101). When there are a plurality of culture chambers 9 to be processed, each culture chamber 9 is placed on a different support base 22.

Around this time, an imaging schedule for each culture chamber 9 is acquired (step S102). This imaging schedule defines when to image the sample contained in each culture chamber 9. The following operations are executed based on this imaging schedule. In addition to the imaging schedule, information defining culture conditions, imaging conditions, and the like may be acquired.

When the scheduled imaging time specified in the imaging schedule for any of the samples stored in the culture chamber 9 stored in the storage unit 2 arrives (step S103), the culture chamber 9 containing the sample is transported. It is taken out from the storage unit 2 by the unit 4 (step S104) and conveyed to the imaging unit 3 (step S105). Even in a state where the culture chamber 9 is supported by the support hand 45 of the transport unit 4, the atmosphere control in the chamber is functioning.

The imaging unit 3 images the sample in the culture chamber 9 under predetermined imaging conditions (step S106). After the imaging is completed, the culture chamber 9 is returned to the original support base 22 by the transport unit 4 (step S107). The above process is repeated until the scheduled imaging schedule is completed (step S108). After the schedule is completed, the culture chamber 9 may be stored in the storage unit 2 as it is, or may be carried out to the outside as needed (step S109). In this way, a series of processes is completed.

3 to 5 are views showing the movement of the transport unit when transporting the culture chamber. Specifically, these figures are diagrams showing the movement of the transport unit 4 in the process of transporting the culture chamber 9 from the storage unit 2 to the imaging unit 3. More specifically, FIG. 3 shows the movement of the transport unit 4 when taking out one culture chamber 9 from the storage unit 2. Further, FIG. 4 shows a transport unit 4 during transport of the culture chamber 9. Further, FIG. 5 shows a transport unit 4 when the culture chamber 9 is transported to the imaging unit 3. In FIG. 3, the components of the transport unit 4 are hatched in order to clearly distinguish the transport unit 4, the storage unit 2, and the culture chamber 9 that overlap each other.

Here, the movement when the culture chamber 9 placed on the uppermost support 22 in the storage unit 2 is conveyed to the imaging unit 3 will be described. However, the culture chamber 9 placed on the other support base 22 can be considered basically in the same manner except that the vertical position of the support hand 45 at the time of taking out is different. Further, the operation when the culture chamber 9 is transferred from the imaging unit 3 to the storage unit 2 can be similarly considered by following the operation described below in reverse.

As shown in the front view in the upper part and the plan view in the lower part of FIG. 3A, when the culture chamber 9 is taken out from the storage unit 2, the transport unit 4 is positioned adjacent to the storage unit 2 in the (−X) direction. .. At this time, the support hand 45 is positioned so that its upper surface is slightly lower than the lower surface of the culture chamber 9. Therefore, at this time, the support hand 45 is located directly below the culture chamber 9 supported by the support base 22. The support hand 45 is provided with a notch 451 that is wider than the width (length in the X direction) of the support base 22. At the time of delivery of the transfer chamber 9, the support base 22 enters the notch portion 451 so that the support hand 45 and the support base 22 do not overlap each other in a plan view, whereby spatial interference between the two is avoided in advance. There is.

From this state, the support hand 45 slightly rises as shown by the white arrow in FIG. 3 (b). Then, when the upper surface of the support hand 45 comes into contact with the lower surface of the culture chamber 9, and the support hand 45 rises further, the culture chamber 9 is lifted from the support base 22 and supported only by the support hand 45. In this way, the culture chamber 9 is released from the support by the support base 22 and can be transported. That is, the culture chamber 9 can be taken out from the storage unit 2 by moving the support hand 45 that supports the culture chamber 9 toward the (−Y) direction.

As shown by the horizontal white arrows in FIG. 4, the base portion 41 horizontally moves along the guide rail 12 in the (−Y) direction, so that the entire transport portion 4 moves in the same direction. As a result, the culture chamber 9 supported by the support hand 45 moves in the (−Y) direction. Further, as shown by the white arrows in the vertical direction in FIG. 4, the slider 44 moves up and down along the guide rail 43 to change the height of the culture chamber 9 supported by the support hand 45, that is, the position in the Z direction. Be changed. By such a combination of horizontal movement and ascending / descending movement, the culture chamber 9 supported by the support hand 45 is conveyed toward the imaging unit 3.

As shown in the front view in the upper part and the plan view in the lower part of FIG. 5A, the transport unit 4 takes an image while the support hand 45 keeps its lower surface at a height that does not contact the objective lens 32 of the image pickup unit 3. The unit 3 is positioned adjacent to the (−X) direction side. At this time, the culture chamber 9 is positioned directly above the objective lens 32 used for imaging. If a mechanism for moving the support hand 45 in the X direction is provided in the transport unit 4, it is possible to align the sample in the culture chamber 9 with the objective lens 32 in the horizontal direction.

As shown by the downward white arrow in FIG. 5B, the lower surface of the culture chamber 9 can be brought close to each other directly above the objective lens 32 by lowering the support hand 45 from the above state. In this state, the imaging process by the imaging unit 3 can be executed. That is, in this embodiment, the sample in the culture chamber 9 while being supported by the support hand 45 is imaged by the imaging unit 3.

As described above, in the imaging system 100 of this embodiment, the support state of the culture chamber 9 is supported in a state of being mounted on the support base 22 of the storage unit 2, or is placed on the support hand 45 of the transport unit 4. It is either supported in the cultivated state. Therefore, if the atmosphere control in the chamber can be executed in the state where the culture chamber 9 is placed on the support base 22 and the state where the culture chamber 9 is placed on the support hand 45, the culture in the chamber is performed during the above-mentioned processing. It becomes possible to maintain the environment continuously. The structure of each part to realize this will be described in detail below.

FIG. 6 is an exploded view showing the structure of the culture chamber. The culture chamber 9 can be roughly divided into a chamber body 91 and a base member 92. The chamber body 91 is a box body formed in a substantially rectangular parallelepiped shape by a transparent material such as glass or a resin material (for example, acrylic resin, polycarbonate, PET), and a sample can be stored in the storage space SP inside the chamber body 91. .. That is, although not shown, a part of the box body can be opened and closed, and the sample can be taken in and out of the accommodation space SP.

Specifically, a sample such as a cell or a fertilized egg to be imaged is supported in a sample container in which an appropriate medium is injected, and the sample container is installed in the chamber body 91. As the sample container, general ones used for culturing cells and the like, for example, dishes, petri dishes, well plates and the like can be preferably applied. In FIG. 6, a state in which two dishes D are placed in the accommodation space SP is shown by a broken line.

The chamber body 91 is fitted in a recess 921 provided according to the shape of the bottom surface of the chamber body 91 on the upper surface of a base member 92 which is a flat plate-like member having a plane size larger than the plane size of the chamber body 91. An opening 922 is provided in the central portion of the recess 921, and when the culture chamber 9 is viewed from below, the bottom surface of the chamber body 91 is exposed facing the opening 922. Since the chamber body 91 is made of a transparent material, it is possible to observe and image the sample in the accommodation space SP through the opening 922.

Further, on the bottom surface of the chamber main body 91, a first connector C1 provided corresponding to the support base 22 and a second connector C2 provided corresponding to the support hand 45 are provided. The first connector C1 is a general term for the air supply connector 93, the exhaust connector 94, and the signal connector 95. These connectors 93 to 95 are provided so as to penetrate the bottom surface of the chamber at positions facing the opening 922 of the base member 92 on the bottom surface of the chamber body 91.

On the other hand, the second connector C2 is a general term for the air supply connector 96, the exhaust connector 97, and the signal connector 98. These connectors 96 to 98 are provided so as to penetrate the bottom surface of the chamber at positions of the bottom surface of the chamber body 91 facing the upper surface of the recess 921 of the base member 92. Corresponding to these connectors, the base member 92 is provided with through holes 923 to 925. Therefore, the connector 96 is opened downward through the through hole 923, the connector 97 is opened through the through hole 924, and the connector 98 is opened downward through the through hole 925.

FIG. 7 is a diagram showing the relationship of the connector between the culture chamber and the support base. More specifically, FIG. 7 (a) is a diagram showing an engagement state between the two connectors when the culture chamber 9 is placed on the support base 22, and FIG. 7 (b) is a diagram showing each air supply. It is a figure which shows the structure of the connector.

When the culture chamber 9 is placed on the support base 22 of the storage unit 2, the first connector C1 engages with the connector provided on the support base 22 side corresponding to these. Specifically, the air supply connector 221 is provided at a position on the upper surface of the support base 22 corresponding to the air supply connector 93 on the culture chamber 9 side. Further, an exhaust connector 222 is provided at a position corresponding to the exhaust connector 94, and a signal connector 223 is provided at a position corresponding to the signal connector 95.

FIG. 7B shows the cross-sectional structure of the air supply connector 93 on the culture chamber 9 side and the air supply connector 221 on the support base 22 side. These connectors are gas connectors that enable gas to flow from the support base 22 side to the accommodation space SP of the culture chamber 9 by engaging with each other. Since the structures of the exhaust connectors 94 and 222 are basically the same as those of the air supply connectors 93 and 221 respectively, the description of these structures will be omitted. Further, as for the signal connectors 95 and 223, those having a general structure used as a connector for transmitting an electric signal can be applied, so that the structural description will be omitted.

First, the structure of the air supply connector 221 on the support base 22 side will be described. The appearance of the air supply connector 221 corresponds to a cross section shown in FIG. 7B rotated around a vertical axis passing through the center, and has a shape rotationally symmetric with respect to the vertical axis. The air supply connector 221 surrounds the base portion 221a attached to or embedded in the upper surface of the support base 22, the plug portion 221b protruding upward from the central portion thereof and having a substantially conical or conical trapezoidal outer shape, and the periphery thereof. It has an annular packing portion 221d provided in. A through hole 221c that functions as a gas flow path is provided along the central axis of the plug portion 221b.

At least the packing portion 221d of the air supply connector 221 is required to be formed of an elastic material that elastically deforms when pressed against the lower surface of the chamber as described later. For example, an elastic rubber material can be applied. The entire air supply connector 221 may be integrally made of a single elastic material.

As shown by the solid line arrow in FIG. 7B, the through hole 221c of the air supply connector 221 is supplied with appropriately adjusted gas from the gas supply unit described later. At least one of the temperature, humidity, and gas composition of the supplied gas is adjusted so as to optimize the culture environment according to the sample in the storage chamber SP. As will be described later, the gas is sent from the air supply connector 221 on the support base 22 side to the accommodation space SP via the air supply connector 93 on the culture chamber 9 side. On the other hand, in the exhaust connector 222 having the same structure, as shown by the dotted arrow, the through hole functions as a flow path for discharging the atmosphere in the accommodation chamber SP to the outside.

Next, the structure of the air supply connector 93 on the culture chamber 9 side will be described. The air supply connector 93 is attached so as to close the through hole 911 provided on the lower surface of the chamber body 91 from the accommodation space SP side. Specifically, a sealing material 931 made of an elastic material having a substantially circular hole in the center is attached to the through hole 911, and a valve 932 is provided so as to cover the upper portion thereof. The valve 932 is swingable around the support shaft 932a, which opens and closes the through hole 911. The valve 932 may be made of an elastic material and may have a structure that opens and closes the through hole 911 by elastically deforming.

FIG. 8 is a cross-sectional view showing how the air supply connector is engaged. When the air supply connector 221 provided on the support base 22 and the air supply connector 93 on the culture chamber 9 side are brought closer to each other with their horizontal positions aligned, FIG. 8A shows. As shown in the above, the upper end of the plug portion 221a of the air supply connector 221 abuts on the lower surface of the valve 932 through a hole provided in the central portion of the sealing material 931 of the air supply connector 93.

When the air supply connector 221 is further raised, the valve 932 is pushed up and begins to open as shown in FIG. 8B, and the through hole 221c of the air supply connector 221 and the accommodation space SP of the culture chamber 9 communicate with each other. At this time, the upper end of the packing portion 221d is brought into contact with the lower surface of the chamber body 91. In this way, since the packing portion 221d, which is an elastic body, adheres to the lower surface of the chamber body 91 and functions to seal the periphery of the through hole 911, it is possible to prevent the accommodation space SP from communicating with the external space.

Finally, as shown in FIG. 8C, the plug portion 221a greatly advances into the accommodation space SP, the valve 932 opens, the outer peripheral portion of the plug portion 221a is sealed by the sealing material 931, and further outside. The through hole 911 is sealed by the packing portion 221d. In this state, an appropriately adjusted gas is supplied from the support base 22 side into the accommodation space SP via the air supply connector 931 and the air supply connector 221.

The structure of the exhaust connector 222 is the same as that of the air supply connector 221 and the structure of the exhaust connector 94 is also the same as that of the air supply connector 93. The engagement state between the exhaust connectors is the same as that of the exhaust connector. The exhaust connector 222 of the support base 22 is connected to an exhaust system (not shown). Therefore, the gas in the accommodation space SP is discharged to the outside via the exhaust connectors 94 and 222.

In this way, in the state where the culture chamber 9 is placed on the support 22 of the storage unit 2, the gas adjusted according to the sample is supplied to the accommodation space SP via the air supply connector, and the excess gas is discharged. By being discharged through the exhaust connector, the gas in the accommodation space SP circulates, and the atmosphere in the accommodation space SP is constantly controlled to the conditions suitable for the sample. Therefore, by storing the culture chamber 9 containing the sample in the storage unit 2, the sample in the chamber can be cultured in a suitable culture environment.

FIG. 9 is a diagram showing the relationship of the connector between the culture chamber and the support hand. More specifically, FIG. 7A is a diagram showing an engagement state between the two connectors when the culture chamber 9 is placed on the support hand 45, and FIG. 9B is a diagram showing the engagement state between the two connectors when the culture chamber 9 is placed on the support hand 45. It is a figure which shows the cross-sectional structure of. The structure of the air supply connector 96 and the exhaust connector 97 provided on the bottom surface of the chamber body 91 is also the same as that of the air supply connector 93. Further, the signal connector 98 is the same as the signal connector 95.

On the other hand, on the upper surface of the support hand 45, the air supply connector 453, the exhaust connector 454, and the signal connector 455 are located at positions corresponding to the air supply connector 96, the exhaust connector 97, and the signal connector 98 in the horizontal direction. Is provided. The structure and function of the air supply connector 453 and the exhaust connector 454 are the same as those of the air supply connector 221 provided on the support base 22. Further, the structure and function of the signal connector 455 are the same as the structure of the signal connector 223 provided on the support base 22.

However, it differs from the engagement of the connector between the support base 22 and the culture chamber 9 in that the engagement between the connectors is performed through the through hole of the base member 92. That is, as shown in FIG. 9B, the air supply connector 453 of the support hand 45 comes into close contact with the lower surface of the chamber body 91 through the through hole 923 provided in the base member 92 and engages with the air supply connector 96. .. Alternatively, as shown in FIG. 9C, the air supply connector 453 may be in close contact with the integrated chamber body 91 and base member 92 on the lower surface thereof.

Similarly, the exhaust connectors 97 and 454 are engaged through the through holes 924, and the signal connectors 98 and 458 are engaged through the through holes 925, respectively. It is not an essential requirement that the connector on the support hand 45 side and the connector on the culture chamber 9 side are engaged with each other via the base member in this way, and the same engagement as in the case of the connector on the support base 22 is performed. It may be a structure that is used.

When the culture chamber 9 is supported by the support hand 45 and the connector is engaged, the adjusted gas is supplied from the support hand 45 side to the accommodation space SP via the air supply connector, and the excess gas is supplied to the exhaust connector. Is discharged through. Therefore, the sample in the chamber can be maintained in a suitable culture environment even during the period when the culture chamber 9 is supported by the support hand 45 and transported or imaged.

10 and 11 are views showing the transfer of the culture chamber from the support base to the support hand. More specifically, FIGS. 10 (a) to 10 (d) and FIGS. 11 (a) to 11 (c) are diagrams schematically showing state changes of each part in the process of delivery, and FIG. 11 (D) is a timing chart showing the operation of the solenoid valve that opens and closes the gas flow path. In these figures, each connector is simplified and shown in order to make the operation easy to see. Further, for convenience of illustration, the description of the signal connector is omitted, and the arrangement of the illustrated connector does not match the actual spatial arrangement in the culture chamber 9.

As shown in these figures, the image pickup system 100 is further provided with solenoid valves V1 to V4 in order to appropriately supply gas to the accommodation space SP and exhaust air from the accommodation space SP. More specifically, the solenoid valve V1 is connected to the air supply connector 453 of the support hand 45, the solenoid valve V2 is connected to the air supply connector 221 of the support base 22, and the solenoid valves V1 and V2 will be described later. Gas is supplied from the gas supply unit. On the other hand, the solenoid valve V3 is connected to the exhaust connector 454 of the support hand 45, the solenoid valve V4 is connected to the exhaust connector 222 of the support base 22, and the solenoid valves V3 and V4 are connected to an exhaust system (not shown). .. In the figure below, among the solenoid valves V1 to V4 that are in the open state, "open" is added in the vicinity thereof. On the other hand, valves without this appendix shall be in the closed state.

FIG. 10A shows a state in which the culture chamber 9 is placed on the support base 22. At this time, the connectors 93, 94, 95 of the culture chamber 9 are engaged with the connectors 221, 222, 223 of the support base 22, respectively (the signal connectors 95, 223 are not shown). As shown in FIG. 11D, at the time T1 in this state, the solenoid valves V1 and V3 are closed and the solenoid valves V2 and V4 are open. Therefore, as shown by an arrow, gas is supplied to the accommodation space SP via the solenoid valve V2 and the air supply connector 221 of the support base 22, and the exhaust from the accommodation space SP is exhausted from the support base 22. This is done via the exhaust connector 222 and the solenoid valve V4.

As shown in FIG. 10B, the support hand 45 rises to receive the culture chamber 9 from the support base 22. As shown in FIG. 11D, before the time T2 when the connectors 453,454,455 on the support hand 45 side come into contact with the connectors 96,97,98 on the chamber side (the signal connectors 98,455 are shown). (Omitted), the open solenoid valves V2 and V4 are closed. As a result, the gas supply to the accommodation space SP and the exhaust from the accommodation space SP are stopped.

As shown in FIGS. 10 (c) to 11 (b), as the support hand 45 rises, the connector on the support hand 45 side and the connector on the culture chamber 9 side are engaged with each other. The engagement between the connector on the support base 22 side and the connector on the culture chamber 9 side is released. Then, as shown in FIG. 11B, the solenoid valves V2 and V4 are set after the time T3 when the engagement between the connector on the support base 22 side and the connector on the culture chamber 9 side is completely disengaged and the delivery is completed. It will be opened. At the time T4 after the opening, gas is supplied from the support hand 45 to the accommodation space SP via the solenoid valve V1 and the air supply connector 453, as shown by arrows in FIG. 11 (c). Further, exhaust from the accommodation space SP is performed via the exhaust connector 454 and the solenoid valve V3.

The operation when the culture chamber 9 after imaging is returned from the support hand 45 to the support base 22 of the storage unit 2 is the opposite of the above. Also at this time, as shown in FIG. 11D, the solenoid valves V1 and V3 are closed earlier than the time T5 when the connector on the support base 22 side engages with the connector on the culture chamber 9 side. Then, the solenoid valves V2 and V4 are opened after the time T6 when the connector on the support hand 45 side and the connector on the culture chamber 9 side are completely disengaged. As a result, gas is supplied and exhausted again through the support base 22.

As described above, in this embodiment, when the culture chamber 9 is handed over between the support base 22 and the support hand 45, the gas supply to the accommodation space SP and the exhaust from the accommodation space SP are temporarily stopped. A blank period BP is provided. This is to suppress the temporary disturbance of the culture environment that may occur when the atmosphere control via the support base 22 and the atmosphere control via the support hand 45 are executed in parallel. The suspension of gas flow for a short period of time when the culture chamber 9 is delivered has almost no effect on the state of the sample. Naturally, it is desirable that the blank period BP be as short as possible.

FIG. 12 is a block diagram showing a control system of this imaging system. As the imaging unit 3 of the imaging system 100, for example, a known microscope imaging device, OCT imaging device, or the like can be applied. As a general configuration of this type of image pickup apparatus, the image pickup unit 3 includes a lighting unit 301 that illuminates an object to be imaged, an image pickup unit 302 that has an image pickup device such as a CCD camera and executes an image pickup operation, and an objective lens 32. It includes an optical system 303, a signal processing unit 304 that processes image data obtained by imaging, and the like. The image data processing may be performed by the control unit 5.

The control unit 5 of the imaging system 100 temporarily stores various data generated by the operation of the CPU (Central Processing Unit) 51 and the CPU 51 that control the operation of each unit by executing a predetermined control program. It includes a memory 52, a storage 53 for storing control programs and various data, and a user interface (UI) 54. These can be realized by a personal computer or workstation having a general configuration. On the other hand, the following blocks are characteristic of the present embodiment, but some of them can be realized by software by the above-mentioned personal computer or the like.

The control unit 5 of the present embodiment includes a transport control unit 551 that controls the operation of the transport unit 45. The transport control unit 551 controls the horizontal movement mechanism 401 that is provided in the transport unit 4 and executes the horizontal movement, and the elevating mechanism 402 that executes the horizontal movement, and realizes the above-mentioned transfer operation. As the horizontal movement mechanism 401 and the elevating mechanism 402, various linear drive mechanisms (not shown) can be used. For example, a linear motor, a ball screw mechanism, a linear motion guide, a rack and pinion mechanism, and the like can be suitably applied.

Further, the control unit 5 is provided with a valve control unit 552 for controlling the opening and closing of the solenoid valves V1 and V3 provided in the transport unit 4, and a gas supply unit 553 for supplying the adjusted gas to the solenoid valve V1. ing. The gas supply unit 553 has a gas supply source and an adjustment function for adjusting at least one of temperature, humidity and gas composition. When the solenoid valves V1 and V3 are opened by a control command from the valve control unit 552, gas flow from the gas supply unit 553 to the transport unit 4 is realized.

When the culture chamber 9 is supported by the transfer unit 4, as shown by the broken line arrow in FIG. 12, the transfer unit 4 and the culture chamber 9 are connected to the connector C2 (air supply connector 93, exhaust) provided in the culture chamber 9. They are connected to each other via the connector 94 and the signal connector 95). The gas flow through the transport unit 4 (more specifically, the support hand 45) is performed via the connector C2.

Further, the culture chamber 9 is provided with an atmosphere sensor 901. The atmosphere sensor 901 detects at least one of the temperature, humidity, and gas composition in the accommodation space SP, and outputs a signal according to the detection result. The output signal from the atmosphere sensor 901 is transmitted to the transport unit 4 via the connector C2, and further transmitted to the atmosphere control unit 554 provided in the control unit 5.

The atmosphere control unit 554 controls the temperature, humidity, composition, etc. of the gas delivered by the gas supply unit 553 based on the output from the atmosphere sensor 901. By feeding back the environment detection result in the accommodation space SP to the adjustment of the supply gas in this way, the atmosphere in the accommodation space SP can be stably controlled.

On the other hand, when the culture chamber 9 is stored in the storage unit 2, the support base 22 and the culture chamber 9 are connected to the connector C1 (air supply connector) provided in the culture chamber 9 as shown by the dotted arrow in FIG. 96, exhaust connector 97, signal connector 98) are connected to each other. The gas flow through the storage unit 2 (more specifically, the support base 22) is performed via the connector C1.

At this time, the output signal from the atmosphere sensor 901 is transmitted from the storage unit 2 to the atmosphere control unit 554 via the connector C1. The control unit 5 is further provided with a gas supply unit 555 that supplies gas to the solenoid valve V2 and a valve control unit 556 that controls the opening and closing of the solenoid valves V2 and V4. The gas supply unit 555 has a gas supply source and an adjustment function for adjusting at least one of temperature, humidity and gas composition. When the solenoid valves V2 and V4 are opened by the control command from the valve control unit 556, gas flow from the gas supply unit 555 to the storage unit 2 is realized.

The atmosphere control unit 554 adjusts the temperature / humidity, composition, etc. of the gas sent out by the gas supply unit 555 based on the detection result of the atmosphere sensor 901. By supplying the gas adjusted in this way to the culture chamber 9, it is possible to control the atmosphere of the accommodation space inside the culture chamber 9 stored in the storage unit 2.

It is possible to store a plurality of culture chambers 9 in the storage unit 2. In this case, it is desirable that the atmosphere is individually controlled for each of the stored culture chambers 9. In order to make this possible, the solenoid valves V2 and V4 of the storage unit 2 are individually provided corresponding to each of the plurality of support bases 22. Correspondingly, the valve control unit 556 of the control unit 5 is also required to individually control the solenoid valves V2 and V4 provided on the support bases 22. Further, the gas supply unit 555 is required to supply individually adjusted gas to the solenoid valve V2 provided on each support base 22.

However, these do not necessarily have to be provided independently for each support base 22 as hardware, and it is sufficient if the atmosphere control of each culture chamber 9 can be controlled independently by, for example, parallel processing by common hardware. Further, as long as the atmospheric conditions required in each chamber are common, the gas supplied to each chamber can be adjusted under a single condition. Even in this case, it is desirable that the solenoid valves V2 and V4 are configured so that the gas flow path can be individually opened and closed for each chamber.

As described above, in the imaging system 100 of this embodiment, the culture chamber 9 stored in the storage unit 2 is transported to the imaging unit 3 by the transporting unit 4 as needed, and the sample in the chamber is imaged by the imaging unit 3. It has the function of doing. The atmosphere of the accommodation space SP in the culture chamber 9 is detected in each of the support base 22 on which the culture chamber 9 is placed in the storage unit 2 and the support hand 45 on which the culture chamber 9 is placed in the transport unit 4. A connector for the signal acquired in the above and a connector for sending the adjusted gas to the accommodation space SP and exhausting the excess gas are provided. Further, connectors C1 and C2 corresponding to these connectors are also provided in the culture chamber 9.

Therefore, when the culture chamber 9 is stored in the storage unit 2, the atmosphere control of the storage space SP is realized via the connector provided on the support base 22 of the storage unit 2. Further, when the culture chamber 9 is held by the transport unit 4, the atmosphere control of the accommodation space SP is realized via the connector provided on the support hand 45 of the transport unit 4. In this way, when the culture chamber 9 is stored in the storage unit 2 and when it is transported by the transport unit 4, the atmosphere in the accommodation space SP can be reliably controlled. Therefore, the problem that the atmosphere is not controlled during transportation and the culture environment of the sample in the chamber is disturbed is avoided.

Further, in this imaging system 3, after the culture chamber 9 is transported to the imaging unit 3 by the transport unit 4, imaging is performed with the culture chamber 9 supported by the support hand 45. Then, as described above, the atmosphere control in the chamber is functioning even when it is placed on the support hand 45. Therefore, the atmosphere in the chamber is continuously controlled until one culture chamber 9 is carried out from the storage unit 2, imaged, and returned to the storage unit 2. As a result, deterioration of the sample due to changes in the culture environment during imaging can be suppressed.

Further, the connectors C1 and C2 provided in the culture chamber 9 are arranged on the bottom surface thereof. Therefore, when the culture chamber 9 is placed at an appropriate position on the support base 22 and the support hand 45 on which the corresponding connector is provided on the upper surface, the connector is automatically engaged. With such a configuration, even when the culture chamber 9 is transferred from the support base 22 to the support hand 45 and from the support hand 45 to the support base 22, the physical chamber transfer operates as a connection switching of the connector. Therefore, it is possible to automatically transfer the culture chamber 9 including taking over the atmosphere control in a short time.

In this case, in this embodiment, the gas supply and the exhaust are temporarily stopped by opening and closing the solenoid valve in order to prevent the plurality of control systems from competing with each other during delivery and the control becomes unstable.

Further, the space range in which atmosphere control is required is only in the accommodation space SP of each culture chamber 9, and the storage unit 2 and the transport unit 4 are not included in the space range. Therefore, the target space for atmosphere control requires a small volume, and stable control can be realized relatively easily.

As described above, in the above embodiment, the support base 22 provided in the storage unit 2 functions as the "holding body for storage" of the present invention, while the support hand 45 provided in the transport unit 4 of the present invention. It functions as a "holding body for transportation". Further, the connector C1 and the connector C2 provided in the culture chamber 9 function as the "first connector" and the "second connector" of the present invention, respectively. Further, the chamber body 91 of the culture chamber 9 corresponds to the "containment chamber" of the present invention.

The present invention is not limited to the above-described embodiment, and various modifications other than those described above can be made without departing from the spirit of the present invention. For example, the structure and arrangement of the connector in the above-described embodiment show some examples thereof, and are not limited thereto.

Further, the atmosphere control of the above embodiment is performed based on the detection result of the atmosphere sensor 901 provided in the culture chamber 9, but instead of this, for example, by constantly sending a gas adjusted to preset conditions. The atmosphere in the chamber may be forcibly maintained at a predetermined condition. In this case, a configuration for detecting the atmosphere in the chamber is not always necessary.

Further, regarding the electrical connection between the culture chamber 9 and the control unit 5, not only the one that transmits the detection signal from the inside of the chamber as described above, but also the electric power such as a heater provided in the chamber is supplied with electric power. There may be a connection to supply.

Further, in the above embodiment, the chamber main body 91 constituting the culture chamber 9 is provided with a connector C1 corresponding to the support base 22 of the storage unit 2 and a connector C2 corresponding to the support hand 45. Instead of this, the base member may be provided with two sets of connectors as described below.

FIG. 13 is a diagram illustrating another structure of the culture chamber. In the description of this modification, the configuration having the same or corresponding structure / function as the above embodiment is designated by the same reference numerals as those of the above embodiment, and detailed description thereof will be omitted. The culture chamber 9a has a chamber body 91a and a base member 92a. The connector C1a corresponding to the connectors 221 to 223 of the support base 22 and the connector C2a corresponding to the connectors 453 to 455 of the support hand 45 are both provided on the base member 92a.

In the base member 92a, the connector C1a and the connector C2a are connected in parallel with each other. Therefore, although the culture chamber 9a as a whole has two connectors, it is sufficient to connect only one system between the base member 92a and the chamber body 91a. Even with such a configuration, the same atmosphere control as in the above embodiment is possible. For example, it is possible to carry out the present invention by utilizing an existing culture chamber having only one input / output port for atmosphere control.

Further, in the above embodiment, the entire chamber body 91 of the culture chamber 9 is made of a transparent material, but at least a transparent window necessary for imaging or visual observation is sufficient, and the entire chamber is covered. It doesn't have to be transparent. Further, if visual confirmation is unnecessary, it is not necessary to be transparent to visible light, and it is sufficient that it is transparent to electromagnetic waves having a wavelength used for imaging.

As described above by exemplifying a specific embodiment, in the present invention, the control unit supplies a gas whose temperature, humidity and composition are adjusted to at least one of the temperature, humidity and composition to the accommodation chamber via the connector. It may be. According to such a configuration, it is possible to adjust the atmosphere in the containment chamber according to the sample.

Further, the control unit may acquire information regarding at least one of temperature and humidity via the connector. By acquiring such information, feedback control can be performed according to the current state of the atmosphere in the accommodation room.

The storage holder is a support base that supports the culture chamber from below by placing the culture chamber on the upper part, and the connector of the storage holder is provided on the upper surface of the storage holder for culturing. When the chamber is placed on the storage retainer, it may be configured to engage with a connector provided on the lower surface of the culture chamber. According to such a configuration, the operation of placing the culture chamber on the storage holder also serves as the operation of connecting the connectors of both, so that the culture chamber is simply placed at an appropriate position on the storage holder. Atmosphere control can also function effectively just by placing.

Similarly, the transport retainer is a support that supports and moves the culture chamber from below by placing the culture chamber on the upper portion, and the connector of the transport retainer is on the upper surface of the transport retainer. It may be provided so as to engage with a connector provided on the lower surface of the culture chamber when the culture chamber is placed on the transport retainer. In this case as well, the atmosphere control can be effectively functioned by placing the culture chamber at an appropriate position on the transport retainer.

Further, the connector of the storage holder engages with the first connector provided in the culture chamber, and the connector of the transport holder is provided in the culture chamber at a position different from that of the first connector. It may be configured to engage with the connector of 2. A configuration is also conceivable in which the connector of the storage holder and the connector of the transport holder are selectively engaged with a set of connectors provided in the culture chamber. However, in this case, since it is necessary to completely disengage one connector before starting the engagement of the other connector, the period during which the atmosphere control is interrupted may be relatively long. .. By providing the first and second connectors individually, it is possible to shorten the period in which each connector is in the disengaged state and minimize the interruption of atmosphere control.

Further, the imaging unit may have a configuration in which the sample in the sample container is imaged while the culture chamber containing the sample container is held by the transport retainer. According to such a configuration, the atmosphere control in the culture chamber is continuously executed by being held by the transport holding body, and imaging can be performed while maintaining this state. Therefore, it is possible to avoid the atmosphere control being stopped at the time of imaging and the culture environment from fluctuating. Therefore, it is particularly suitable for repeated imaging while continuing the culture in a constant culture environment.

Further, the imaging unit may have a configuration in which the sample is imaged through a window unit provided in the culture chamber and transparent to electromagnetic waves used for imaging. According to such a configuration, it is not necessary to take out the sample from the culture chamber at the time of imaging, and the sample is always kept in the culture chamber whose atmosphere is controlled, so that it is possible to avoid a change in the culture environment of the sample.

The present invention is particularly effective for the purpose of regularly observing a sample such as cells continuously cultured in a container, and can be widely used in the fields of medicine and drug discovery.

2 Storage unit 3 Imaging unit 4 Transport unit 5 Control unit 9 Culture chamber 22 Support stand (holding body for storage)
45 Support hand (holding body for transportation)
93,96,221,453 Air supply connector 94,97,222,454 Exhaust connector 95,98,223,455 Signal connector 100 Imaging system C1 First connector C2 Second connector

Claims (8)

An imaging unit that captures images of the sample supported on the sample container,
A storage unit for storing a culture chamber having a storage chamber capable of containing the sample container, and a storage unit.
A transport unit that transports the culture chamber in which the sample container is housed between the storage unit and the imaging unit, and a transport unit.
It is provided with a control unit that controls the atmosphere in the accommodation space.
The storage unit has a storage body that holds the culture chamber detachably.
The transport unit has a transport retainer that holds the culture chamber when the culture chamber is transported.
Each of the storage retainer and the transport retainer has a connector that is connected to the containment space when holding the culture chamber.
The control unit controls the atmosphere of the culture chamber held by the storage holder via the connector of the storage holder, and holds the culture chamber held by the transport holder. An imaging system that controls the atmosphere via the connector of the transport holding body. The imaging system according to claim 1, wherein the control unit supplies a gas whose temperature, humidity, and composition are adjusted to the accommodation chamber via the connector. The imaging system according to claim 1 or 2, wherein the control unit acquires information regarding at least one of temperature and humidity via the connector. The storage holder is a support base that supports the culture chamber from below by placing the culture chamber on the upper part.
The connector of the storage retainer is provided on the upper surface of the storage retainer and engages with a connector provided on the lower surface of the culture chamber when the culture chamber is placed on the storage retainer. The imaging system according to any one of claims 1 to 3. The transport retainer is a support that supports and moves the culture chamber from below by placing the culture chamber on the upper part.
The connector of the transport retainer is provided on the upper surface of the transport retainer and engages with a connector provided on the lower surface of the culture chamber when the culture chamber is placed on the transport retainer. The imaging system according to any one of claims 1 to 4. The connector of the storage retainer engages with a first connector provided in the culture chamber, and the connector of the transport retainer is located in the culture chamber at a position different from that of the first connector. The imaging system according to any one of claims 1 to 5, which engages with a second connector provided. The imaging system according to any one of claims 1 to 6, wherein the imaging unit images the sample in the sample container while the culture chamber containing the sample container is held by the transport retainer. .. The imaging system according to claim 7, wherein the imaging unit captures the sample through a window provided in the culture chamber that is transparent to electromagnetic waves used for imaging.

Images