JP7757638B2 - Manipulation System - Google Patents

Description

The present invention relates to a manipulation system.

Cell culture incubators that can maintain a cell culture environment are known. Patent Document 1 describes an incubator device that is installed on a microscope stage and allows cells to be cultured while being observed under the microscope. Patent Document 2 describes a cell culture incubator with a built-in cell manipulation system inside the incubator.

JP 2011-200223 A Special table 2018-510659 publication

Such cell culture incubators are sealed to maintain an internal environment suitable for cell culture. This means that manipulation tools such as manipulators may not be accessible from the outside, making it difficult to manipulate cells while continuing to culture them.

The present invention was made in consideration of the above, and aims to provide a manipulation system that can effectively manipulate cells while maintaining the cell culture environment.

A manipulation system according to one aspect of the present invention comprises a sample stage, a cell culture incubator placed on the sample stage and capable of maintaining a cell culture environment, a manipulator placed inside the cell culture incubator and equipped with a container for containing the cells and a pipette for manipulating the cells, the cell culture incubator having an opening for inserting the pipette into its internal space and a sealing member for sealing the gap between the outer edge of the opening and the pipette.

In this way, the manipulation system can maintain a good environment inside the cell culture incubator because the internal space of the cell culture incubator is sealed off from the outside by the sealing member. A pipette is inserted into the internal space through an opening in the cell culture incubator, allowing cells to be manipulated well while maintaining the cell culture environment in the specified environment inside the cell culture incubator. Furthermore, because the moving parts of the manipulator, such as the drive unit, are located outside the cell culture incubator, exposure to the environment inside the cell culture incubator (e.g., a high-temperature, high-humidity environment) can be reduced.

In one aspect of the present invention, the sealing member is provided in a bellows-like shape so that it can expand and contract. This allows the sealing member to expand and contract in response to the movement of the pipette when manipulating cells by moving the pipette within the internal space. This allows the manipulation system to effectively seal the gap between the outer edge of the opening and the pipette, enabling cell manipulation while maintaining the environment within the cell culture incubator.

A manipulation system according to one aspect of the present invention includes a pipette holding member that holds the pipette, and the sealing member is provided to surround the periphery of the pipette holding member. This allows the manipulation system to effectively seal the gap between the outer edge of the opening and the pipette holding member, thereby maintaining a good environment within the cell culture incubator.

A manipulation system according to one aspect of the present invention includes an imaging unit disposed above the sample stage and the cell culture incubator, and at least the portion of the top plate of the cell culture incubator that overlaps with the imaging unit is formed of a light-transmitting material. This allows the internal space of the cell culture incubator to be observed through the light-transmitting region using a microscope. Therefore, the manipulation system can effectively manipulate cells within the internal space of the cell culture incubator.

In one aspect of the present invention, the cell culture incubator in the manipulation system has at least one through-hole for installing at least one of a sensor or a heater in the internal space. This allows for appropriate control of the environment in the internal space of the cell culture incubator.

In one aspect of the present invention, the manipulation system includes at least the sensor and the heater inside the cell culture incubator, and is connected to the outside through the through-hole. This allows the environment of the internal space of the cell culture incubator to be appropriately controlled.

The present invention provides a manipulation system that can effectively manipulate cells while maintaining the cell culture environment.

FIG. 1 is a diagram schematically illustrating an example of the configuration of a manipulation system according to an embodiment. FIG. 2 is a cross-sectional view showing an example of a fine movement mechanism. FIG. 3 is a control block diagram of the manipulation system. FIG. 4 is a perspective view illustrating the arrangement of the cell culture incubator, the pipette holding member, and the pipette. FIG. 5 is a cross-sectional view taken along line V-V' in FIG. FIG. 6 is a cross-sectional view for explaining an example of the configuration of the mounting member.

Modes for carrying out the present invention (embodiments) will be described in detail with reference to the drawings. The present invention is not limited to the contents described in the following embodiments. Furthermore, the components described below include those that would be easily imagined by a person skilled in the art and those that are substantially identical. Furthermore, the components described below can be combined as appropriate.

(Embodiment)
FIG. 1 is a diagram schematically illustrating the configuration of a manipulation system according to an embodiment. The manipulation system 10 is a system for manipulating a sample, which is a micro-object, under microscope observation. As shown in FIG. 1, the manipulation system 10 includes a microscope unit 12, a first manipulator 14, a second manipulator 16, and a controller 43 that controls the manipulation system 10. The first manipulator 14 and the second manipulator 16 are separately arranged on either side of the microscope unit 12. The micro-object is, for example, a cell or an egg, and will be referred to as a "cell" in the following description.

The microscope unit 12 includes a camera 18 (imaging section) including an image sensor, a microscope 20, and a sample stage 22. A cell culture incubator 60 is placed on the sample stage 22. A sample holding member 11, such as a petri dish, is housed inside the cell culture incubator 60.

The cell culture incubator 60 is a box-shaped component having an internal space. The internal space of the cell culture incubator 60 is sealed and isolated from the outside of the cell culture incubator 60. The internal space of the cell culture incubator 60 is maintained and controlled at a predetermined environment (temperature, carbon dioxide (CO ₂ ) concentration, humidity, etc.) for culturing cells. The cell culture environment is, for example, a temperature of 37°C, a CO ₂ concentration of 5%, and a humidity of 95% or higher. Note that in this specification, "sealed" and "sealed" do not necessarily mean that the internal space of the cell culture incubator 60 is completely sealed off from the outside, but rather means that the internal space of the cell culture incubator 60 is airtight enough to maintain a predetermined environment when the second pipette 35 and the sample stage 22 are moved to manipulate cells.

The microscope 20 is placed directly above the sample stage 22 and cell culture incubator 60. The microscope unit 12 has an integrated structure in which the microscope 20 and camera 18 are integrated, and is equipped with a light source (not shown) that irradiates light toward the sample holding member 11. Note that the camera 18 may be provided separately from the microscope 20.

The sample holding member 11 contains a solution containing cells. Light is irradiated onto the cells in the sample holding member 11, and the light reflected by the cells in the sample holding member 11 enters the microscope 20. An optical image of the cells is magnified by the microscope 20 and then captured by the camera 18. The microscope unit 12 is able to observe the cells based on the image captured by the camera 18.

As shown in FIG. 1, the first manipulator 14 includes a first pipette holding member 24, an X-Y axis table 26, a Z-axis table 28, a drive unit 30 that drives the X-Y axis table 26, and a drive unit 32 that drives the Z-axis table 28. The first manipulator 14 is a three-axis manipulator with an X-axis, Y-axis, and Z-axis configuration.

In this embodiment, one direction within a horizontal plane is defined as the X-axis direction, the direction intersecting the X-axis direction within the horizontal plane is defined as the Y-axis direction, and the direction intersecting both the X-axis direction and the Y-axis direction (i.e., the vertical direction) is defined as the Z-axis direction. The surface of the sample stage 22 is parallel to the XY plane and perpendicular to the Z-axis direction.

The X-Y axis table 26 is movable in the X-axis or Y-axis direction by the drive unit 30. The Z-axis table 28 is arranged on the X-Y axis table 26 so that it can move up and down, and is movable in the Z-axis direction by the drive unit 32. The drive units 30 and 32 are connected to the controller 43.

The first pipette holding member 24 is connected to the Z-axis table 28, and has a first pipette 25, which is a capillary tip, attached to its tip. The first pipette holding member 24 can move in three-dimensional space as a moving area in accordance with the movement of the X-Y axis table 26 and the Z-axis table 28. The first pipette holding member 24 can hold cells contained in the sample holding member 11 via the first pipette 25. In other words, the first manipulator 14 is a holding manipulator used to hold micro-objects, and the first pipette 25 is a holding pipette used as a means for holding micro-objects.

The second manipulator 16 includes a second pipette holding member 34, an X-Y axis table 36, a Z-axis table 38, a drive unit 40 that drives the X-Y axis table 36, and a drive unit 42 that drives the Z-axis table 38. The second manipulator 16 is a three-axis manipulator with an X-axis, Y-axis, and Z-axis configuration.

The XY-axis table 36 can be moved in the X-axis or Y-axis direction by driving a drive unit 40. The Z-axis table 38 is arranged on the XY-axis table 36 so that it can move up and down, and can be moved in the Z-axis direction by driving a drive unit 42. The drive units 40 and 42 are connected to a controller 43.

The second pipette holding member 34 is connected to the Z-axis table 38, and has a second glass pipette 35 attached to its tip. The second pipette holding member 34 can move in three-dimensional space as a moving area in accordance with the movement of the X-Y axis table 36 and the Z-axis table 38. The second pipette holding member 34 is capable of artificially manipulating cells held in the sample holding member 11. In other words, the second manipulator 16 is a manipulation manipulator used to manipulate micro-objects (such as injecting DNA solutions or drilling holes), and the second pipette 35 is an injection pipette used as a means for injecting micro-objects.

The X-Y axis table 36 and Z axis table 38 are configured as a coarse movement mechanism (three-dimensional movement table) that coarsely moves the second pipette holding member 34 to an operation position for cells or the like contained in the sample holding member 11. Furthermore, a fine movement mechanism 44 is provided as a nanopositioner at the connection between the Z axis table 38 and the second pipette holding member 34. The fine movement mechanism 44 supports the second pipette holding member 34 so that it can move in its longitudinal direction (axial direction), and is configured to finely move the second pipette holding member 34 along its longitudinal direction (axial direction).

Figure 2 is a cross-sectional view showing an example of a micromotion mechanism. As shown in Figure 2, the micromotion mechanism 44 includes a piezoelectric actuator 44a that drives the second pipette holding member 34. The piezoelectric actuator 44a includes a cylindrical housing 87, rolling bearings 80 and 82 provided inside the housing 87, and a piezoelectric element 92. The second pipette holding member 34 is inserted axially through the housing 87. The rolling bearings 80 and 82 rotatably support the second pipette holding member 34. The piezoelectric element 92 expands and contracts along the longitudinal direction of the second pipette holding member 34 in response to an applied voltage. The second pipette 35 (see Figure 1) is attached and fixed to the tip side (left side of Figure 2) of the second pipette holding member 34.

The second pipette holding member 34 is supported on the housing 87 via rolling bearings 80 and 82. The rolling bearing 80 includes an inner ring 80a, an outer ring 80b, and a ball 80c located between the inner ring 80a and the outer ring 80b. The rolling bearing 82 includes an inner ring 82a, an outer ring 82b, and a ball 82c located between the inner ring 82a and the outer ring 82b. Each of the outer rings 80b and 82b is fixed to the inner surface of the housing 87, and each of the inner rings 80a and 82a is fixed to the outer surface of the second pipette holding member 34 via a hollow member 84. In this way, the rolling bearings 80 and 82 rotatably support the second pipette holding member 34.

A flange portion 84a protruding radially outward is provided at approximately the center of the hollow member 84 in the axial direction. The rolling bearing 80 is positioned toward the tip of the second pipette holding member 34 relative to the flange portion 84a, and the rolling bearing 82 is positioned toward the rear end of the flange portion 84a. The inner ring 80a of the rolling bearing 80 and the inner ring 82a of the rolling bearing 82 are positioned across the flange portion 84a, which serves as an inner ring spacer. The outer peripheral surface of the second pipette holding member 34 is threaded, and lock nuts 86, 86 are threaded onto the second pipette holding member 34 from the tip end of the inner ring 80a and the rear end of the inner ring 82a. This fixes the axial positions of the rolling bearings 80, 82.

The annular spacer 90 is arranged coaxially with the rolling bearings 80, 82, on the axial rear end side of the outer ring 82b. An annular piezoelectric element 92 is arranged approximately coaxially with the spacer 90 on the axial rear end side of the spacer 90. Furthermore, a lid 88 of the housing 87 is arranged on the axial rear end side of the piezoelectric element 92. The lid 88 is used to fix the piezoelectric element 92 in the axial direction and has a hole through which the second pipette holding member 34 is inserted. The lid 88 may be fastened to the side of the housing 87, for example, with a bolt (not shown). The piezoelectric elements 92 may be rod-shaped or rectangular pillar-shaped and arranged approximately evenly around the periphery of the spacer 90, or may be rectangular tubes with a hole through which the second pipette holding member 34 is inserted.

The piezoelectric element 92 is in contact with the rolling bearing 82 via a spacer 90. The piezoelectric element 92 is connected to the controller 43 via lead wires (not shown). The piezoelectric element 92 expands and contracts axially in response to the applied voltage from the controller 43, finely moving the second pipette holding member 34 along its axial direction. When the second pipette holding member 34 moves finely along its axial direction, this fine movement is transmitted to the second pipette 35 (see Figure 1), thereby finely adjusting the position of the second pipette 35. Furthermore, when the second pipette holding member 34 vibrates axially due to the piezoelectric element 92, the second pipette 35 also vibrates axially. In this way, the fine movement mechanism 44 enables more accurate operations on micro-objects (such as injection and perforation of DNA solutions or cells), improving the perforation action of the piezoelectric element 92.

Note that although the fine movement mechanism 44 described above is provided on the second manipulator 16 for manipulating the micro-object, it may also be provided on the first manipulator 14 for fixing the micro-object, or may be omitted.

Next, the control of the manipulation system 10 by the controller 43 will be explained with reference to Figure 3. Figure 3 is a control block diagram of the manipulation system.

The controller 43 includes hardware resources such as a CPU (Central Processing Unit) as a calculation means, and a hard disk, RAM (Random Access Memory), and ROM (Read Only Memory) as storage means. The controller 43 performs various calculations based on predetermined programs stored in the storage unit 46B, and outputs drive signals so that the control unit 46A performs various controls according to the calculation results.

The control unit 46A is a control circuit that controls the focusing mechanism 81 of the microscope unit 12, the drive unit 30, drive unit 32, suction pump 29 of the first manipulator 14, and the drive unit 40, drive unit 42, piezoelectric element 92, and injection pump 39 of the second manipulator 16. The control unit 46A outputs drive signals to the microscope unit 12, the first manipulator 14, and the second manipulator 16 via drivers, amplifiers, etc., provided as necessary. The control unit 46A supplies drive signals Vxy and Vz (see Figure 1) to the drive units 30, 32, 40, and 42, respectively. The drive units 30, 32, 40, and 42 drive in the X-, Y-, and Z-axis directions based on the drive signals Vxy and Vz. The control unit 46A may also control the fine movement mechanism 44 by supplying a nanopositioner control signal VN (see Figure 1) to the fine movement mechanism 44.

The controller 43 is connected to a joystick 47 as information input means and an input unit 49. The input unit 49 is, for example, a keyboard, touch panel, mouse, etc. The controller 43 is also connected to a display unit 45 such as an LCD panel. The display unit 45 displays microscope images acquired by the camera 18 and various control screens. If a touch panel is used as the input unit 49, the touch panel may be superimposed on the display screen of the display unit 45 so that the operator can perform input operations while checking the image displayed on the display unit 45.

A known joystick 47 can be used. The joystick 47 includes, for example, a base and a handle portion that stands upright from the base. The joystick 47 can perform X-Y drive of the drive units 30, 40 by tilting the handle portion, and can perform Z drive of the drive units 32, 42 by twisting the handle portion. The joystick 47 may also include buttons for controlling the drive of the suction pump 29, the piezoelectric element 92, and the injection pump 39.

The controller 43 further includes an image input unit 43A, an image processing unit 43B, an image output unit 43C, and a position detection unit 43D. An image signal V _PIX (see FIG. 1) captured by the camera 18 through the microscope 20 is input to the image input unit 43A. The image processing unit 43B receives the image signal from the image input unit 43A and performs image processing. The image output unit 43C outputs the image information processed by the image processing unit 43B to the display unit 45. The position detection unit 43D can detect the position of a micro-object such as a cell or a cell nucleus based on the image information after image processing. The cell nucleus is the object to be injected by the second pipette 35. The position detection unit 43D can detect the presence or absence of a cell or the like within the imaging area of the camera 18 based on the image information. The position detection unit 43D may also detect the positions of the first pipette 25 and the second pipette 35. The image input unit 43A, the image processing unit 43B, the image output unit 43C, and the position detection unit 43D are controlled by a control unit 46A.

The image processing unit 43B performs binarization and filtering on the image signal received from the image input unit 43A to detect, for example, the position of a cell or the position of a cell nucleus. The image processing unit 43B converts the image signal into a grayscale image based on a predetermined threshold value that has been set in advance. The image processing unit 43B then performs edge extraction and pattern matching on the monochrome image obtained by the binarization and filtering processes. The position detection unit 43D can detect the position of a cell or the position of a cell nucleus based on the results of this processing.

The control unit 46A controls the first manipulator 14 and the second manipulator 16 based on position information from the position detection unit 43D and information on the presence or absence of cells, etc. In this embodiment, the control unit 46A automatically drives the first manipulator 14 and the second manipulator 16 in a predetermined sequence. This sequential driving is performed by the control unit 46A outputting drive signals to each manipulator in sequence based on the results of calculations by the CPU using a predetermined program stored in advance in the memory unit 46B.

Next, the detailed configuration of the cell culture incubator 60 will be described. Figure 4 is a perspective view illustrating the relative positions of the cell culture incubator, pipette holding member, and pipette. Figure 5 is a cross-sectional view taken along the V-V' line in Figure 4. Note that Figures 4 and 5 show the opening OP and sealing member 70 corresponding to the second pipette holding member 34 and second pipette 35, and do not illustrate the opening OP and sealing member 70 on the first pipette holding member 24 and first pipette 25 side. However, the description of the opening OP and sealing member 70 in Figures 4 and 5 can also be applied to the opening OP and sealing member 70 corresponding to the first pipette holding member 24 and first pipette 25.

As shown in Figures 4 and 5, the cell culture incubator 60 has a bottom plate 61 and a cover portion 62. The bottom plate 61 is a flat member and is positioned opposite the upper surface of the sample stage 22 (see Figure 1). The cover portion 62 has a top plate 62a and a side plate 62b. The lower portion of the side plate 62b is connected to the bottom plate 61, sealing the internal space of the cell culture incubator 60.

As shown in FIG. 4, the cell culture incubator 60 has a rectangular shape when viewed from above. However, this is not limited to this, and the cell culture incubator 60 may have other shapes, such as a polygonal shape or a circular shape.

As shown in Figures 4 and 5, an opening OP is provided in the side plate 62b of the cell culture incubator 60. As described above, the second pipette 35 and the second pipette holding member 34 are inserted into the internal space of the cell culture incubator 60 through the opening OP. The opening OP is circular when viewed from the side (X-axis direction). The diameter of the opening OP is larger than the diameters of the second pipette 35 and the second pipette holding member 34. The opening OP is located on the upper side (top plate 62a side) of the side plate 62b. More specifically, the opening OP is located at least above the sample holding member 11. This allows the manipulation system 10 to move the second pipette holding member 34 within the opening OP, thereby manipulating cells in the cell culture incubator 60.

The position, size, and shape of the opening OP can be changed as appropriate. For example, the opening OP is not limited to being provided on the side plate 62b, but may be provided on the top plate 62a. Furthermore, the opening OP is not limited to being circular, but may be other shapes such as elliptical, polygonal, or rectangular. The opening OP can be of an appropriate shape depending on the cell manipulation.

A sealing member 70 is provided to cover the opening OP. The sealing member 70 seals the gap between the outer edge of the opening OP and the second pipette holding member 34 (and the second pipette 35). The sealing member 70 is attached to the outer periphery of the second pipette holding member 34 by an attachment member 71.

The sealing member 70 is configured to be expandable and contractible in an accordion-like manner. Specifically, the sealing member 70 is formed from a flexible material, such as a resin film material such as nylon or vinyl, or a sheet-like rubber. One end of the sealing member 70 is fixed to the outer periphery of the second pipette holding member 34, and the other end of the sealing member 70 is fixed to the side panel 62b of the cell culture incubator 60 at the outer edge of the opening OP. The sealing member 70 is configured to be deformable when the second pipette holding member 34 (and the second pipette 35) moves within the opening OP.

Figure 6 is a cross-sectional view illustrating an example configuration of the mounting member. The mounting member 71 has a first nut 72 and a second nut 73. The outer peripheral surface of the second pipette holding member 34 is threaded, and the first nut 72 and second nut 73 are screwed onto the second pipette holding member 34. The sealing member 70 and O-ring 74 are sandwiched between the first nut 72 and the second nut 73 in the axial direction of the second pipette holding member 34. This creates a seal between the second pipette holding member 34 and the sealing member 70.

More specifically, the first nut 72 has a protrusion 72a protruding from the underside of the first nut 72. The protrusion 72a is formed in a ring shape that surrounds the second pipette holding member 34. The second nut 73 has a protrusion 73a protruding from the upper surface of the second nut 73. The protrusion 73a of the second nut 73 is formed in a ring shape that surrounds the outer periphery of the protrusion 72a of the first nut 72. The sealing member 70 and O-ring 74 are disposed in a recess formed between the protrusion 73a of the second nut 73 and the outer periphery of the second pipette holding member 34. When the first nut 72 and the second nut 73 rotate in directions that bring them closer to each other, the sealing member 70 and O-ring 74 are sandwiched between the protrusion 72a and the second nut 73, which forms the bottom of the recess.

Note that the configuration of the mounting member 71 shown in Figure 6 is merely one example. The mounting member 71 may have any structure as long as it is configured to seal the gap between the second pipette holding member 34 and the sealing member 70. For example, the protrusions 72a and 73a may be omitted. Although not shown, the sealing between the opening OP and the sealing member 70 may also have any structure as long as the sealing member 70 is fixed along the outer edge of the opening OP, along the side panel 62b of the cell culture incubator 60, and can seal the opening OP. The sealing member 70 may simply be adhered to the second pipette holding member 34 with an adhesive. Alternatively, the sealing member 70 may be clamped to the second pipette holding member 34 with a clamping member.

Next, returning to Figures 4 and 5, at least the portion of the top plate 62a of the cell culture incubator 60 that overlaps with the camera 18 (see Figure 1) of the microscope unit 12 is made of a light-transmitting material. The light-transmitting material may be, for example, glass. A portion of the top plate 62a may be made of a light-transmitting material, or the entire top plate 62a may be made of a light-transmitting material. This allows the manipulation system 10 to observe the second pipette 35 and cells in the internal space of the cell culture incubator 60 using the camera 18 through the light-transmitting region of the top plate 62a.

Note that the cell culture incubator 60 is composed of two components (a bottom plate 61 and a cover 62), but is not limited to this. The cell culture incubator 60 may also be composed of three components, for example, a bottom plate, a top plate, and a side plate, which are connected together. Depending on the positional relationship with the sample stage 22 and the manipulator, the cell culture incubator 60 may also be composed of four or more components.

Furthermore, the cell culture incubator 60 is not limited to having an opening OP, and may also have through-holes (not shown) for installing heaters and various sensors in the internal space of the cell culture incubator 60. For example, wiring connected to the heater or various sensors is inserted into the through-hole. In this case, the manipulation system 10 of this embodiment can easily adjust and manage the environment inside the cell culture incubator 60 via the through-hole.

As described above, the manipulation system 10 of this embodiment includes a sample stage 22, a cell culture incubator 60 that is placed on the sample stage 22 and can maintain a cell culture environment, a sample holding member 11 (container) that is placed inside the cell culture incubator 60 and that contains cells, and a second manipulator 16 that is equipped with a pipette (e.g., a second pipette 35) for manipulating the cells. An opening OP is provided in the side panel 62b of the cell culture incubator 60 for inserting the second pipette 35 into the internal space, and a sealing member 70 is provided to seal the gap between the outer edge of the opening OP and the second pipette 35.

In this way, the manipulation system 10 can maintain a good environment within the cell culture incubator 60 because the sealing member 70 shields the internal space of the cell culture incubator 60 from the outside. The second pipette 35 is inserted into the internal space through the opening OP provided in the cell culture incubator 60, allowing cells to be manipulated well within the cell culture incubator 60 while maintaining the cell culture environment. In other words, cells can be manipulated using the second manipulator 16 while continuing to culture the cells in the cell culture incubator 60 for an extended period of time without being exposed to the atmosphere. Furthermore, the moving parts of the second manipulator 16, such as the drive units 40 and 42, are located outside the cell culture incubator 60, preventing them from being exposed to the environment within the cell culture incubator 60 (e.g., a high-temperature, high-humidity environment). Therefore, the manipulation system 10 can prevent corrosion and rust from occurring in the moving parts of the second manipulator 16, such as the drive units 40 and 42.

In addition, in the manipulation system 10 of this embodiment, the sealing member 70 is provided in an accordion-like manner so that it can expand and contract. Therefore, when the second pipette 35 is moved within the internal space to manipulate cells, the sealing member 70 is provided so that it can expand and contract in accordance with the movement of the second pipette 35. This allows the manipulation system 10 to effectively seal the gap between the outer edge of the opening OP and the second pipette 35, allowing cell manipulation to be performed while maintaining the environment within the cell culture incubator 60.

The manipulation system 10 of this embodiment also includes a second pipette holding member 34 that holds the second pipette 35, and the sealing member 70 is provided to surround the periphery of the second pipette holding member 34. This allows the manipulation system 10 to effectively seal the gap between the outer edge of the opening OP and the second pipette holding member 34, thereby maintaining a good environment within the cell culture incubator 60.

The manipulation system 10 of this embodiment also includes a camera 18 (imaging unit) positioned above the sample stage 22 and the cell culture incubator 60, and at least the portion of the top plate 62a of the cell culture incubator 60 that overlaps with the camera 18 is made of a light-transmitting material. This allows the camera 18 to observe the internal space of the cell culture incubator 60 through the light-transmitting region. Therefore, the manipulation system 10 can effectively manipulate cells in the internal space of the cell culture incubator 60.

10 Manipulation system 11 Sample holding member 12 Microscope unit 14 First manipulator 16 Second manipulator 18 Camera 20 Microscope 22 Sample stage 24 First pipette holding member 25 First pipette 26, 36 XY axis table 28, 38 Z axis table 30, 32, 40, 42 Driving device 34 Second pipette holding member 35 Second pipette 43 Controller 44 Fine movement mechanism 46A Control unit 60 Cell culture incubator 61 Bottom plate 62 Cover part 62a Top plate 62b Side plate 70 Sealing member 71 Mounting member OP Opening

Claims (4)

a sample stage;
a cell culture incubator that is placed on the sample stage and can maintain a cell culture environment;
a container placed inside the cell culture incubator for containing the cells;
a manipulator having a pipette for manipulating the cells;
the cell culture incubator is provided with an opening for inserting the pipette into an internal space;
a sealing member is provided to seal a gap between an outer edge of the opening and the pipette ;
the manipulator has a pipette holding member that holds the pipette;
the sealing member is bellows-shaped and is provided so as to be expandable and contractible in accordance with the movement of the pipette;
One end of the sealing member is fixed to the outer periphery of the pipette holding member, and the other end of the sealing member is fixed to the opening of the cell culture incubator.
Manipulation system. an imaging unit disposed above the sample stage and the cell culture incubator;
The manipulation system according to claim 1 , wherein at least a portion of the top plate of the cell culture incubator that overlaps with the imaging unit is made of a light-transmitting material. 3. The manipulation system according to claim 1 , wherein the cell culture incubator has at least one through-hole for installing at least one of a sensor and a heater in the internal space. The manipulation system according to claim 3 , wherein at least the sensor and the heater are provided inside the cell culture incubator and are connected to the outside through the through-hole.