Optical microscope

Abstract

To make it easy to capture again a place once removed from the visual field of a microscope in the visual field.SOLUTION: An optical microscope including an objective lens, a stage on which an object is placed, a stage driving unit configured to move the stage in a plane orthogonal to an optical axis of the objective lens, an imaging unit configured to capture an image of the object through the objective lens, a storage unit configured to store a position of the stage at a predetermined timing and additional information that is information based on an image captured by the imaging unit at the timing in association with each other, a display control unit configured to cause a display device to display position selection information including the additional information, a selection reception unit configured to receive an operation of selecting the position selection information, A stage control unit 401 configured to control the stage driving unit to move the stage to a position stored in the storage unit in association with the additional information included in the position selection information selected via the selection receiving unit.SELECTED DRAWING: Figure 3

Description

[Technical Field]

[0001] The present invention relates to an optical microscope. [Background technology]

[0002] An optical microscope (hereinafter sometimes simply referred to as a microscope) generally includes an objective lens, an eyepiece, and a stage on which an object to be observed is placed. When observing an object to be observed using a microscope, a user operates the stage to change the part of the object to be observed that is included in the observation field of the microscope, and visually observes a magnified image of the object to be observed through the objective lens and the eyepiece.

[0003] Also known as a microscope-based device is a cell picking device that assists in the operation of picking a collection target, such as a specific cell, from a container such as a petri dish and transferring it to another container (see, for example, Patent Document 1). The cell picking device includes, for example, a microscope equipped with a stage and an aspirating device that aspirates cells from a container such as a petri dish placed on the stage and dispenses them into another container (for example, a specified well on a microplate). The aspirating device includes an aspirating arm to which a pipette tip is attached and a driving unit that moves the aspirating arm and causes the aspirating arm to perform aspirating and dispensing operations.

[0004] When using the cell picking device described above to pick cells from a container such as a petri dish, the container is first placed on a stage, and the stage is moved while observing under a microscope to search for the cell to be picked. Once the cell to be picked is determined, the suction arm is moved to bring the tip of the pipette tip attached to the suction arm close to the cell to be picked, while the cell is captured within the field of view of the microscope. The suction arm then performs a suction operation to suck the cell into the pipette tip. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Patent No. 7255687 Summary of the Invention [Problem to be solved by the invention]

[0006] In the process of observing an object using a microscope or searching for cells to be collected using a cell picking device including a microscope, there are cases where a location that has been removed from the observation field of the microscope is desired to be recaptured within the observation field. However, under high magnification, it is generally difficult to recapture a location that has been removed from the microscope's field of view within the observation field.

[0007] The present invention has been made in consideration of the above points, and its object is to make it possible to easily capture an area that has once been removed from the field of view of a microscope back into the field of view. [Means for solving the problem]

[0008] The optical microscope according to the present invention, which has been made to solve the above problems, comprises: An objective lens, a stage on which an object is placed; a stage driving unit that moves the stage within a plane perpendicular to the optical axis of the objective lens; an imaging unit that images the object through the objective lens; a storage unit that stores a position of the stage at a predetermined timing in association with additional information based on an image captured by the imaging unit at the predetermined timing; a display control unit that causes a display device to display position selection information including the additional information; a selection receiving unit that receives an operation to select the position selection information displayed on the display device; a stage control unit that controls the stage driving unit to move the stage to the selected position, which is the position stored in the storage unit in association with the additional information included in the position selection information selected via the selection receiving unit; It has the following characteristics. [Effects of the Invention]

[0009] According to the optical microscope of the present invention having the above-mentioned configuration, the user can simply select an appropriate one from the position selection information displayed on the display device, and the stage can be automatically moved to the position corresponding to the position selection information (i.e., the selected position). This makes it easy to bring a location that has once been removed from the field of view of the microscope back into the field of view. [Brief explanation of the drawings]

[0010] [Figure 1] FIG. 1 is a front view of a cell picking device according to an embodiment of the present invention. [Figure 2] FIG. 2 is a schematic configuration diagram of a microscope unit in the embodiment. [Figure 3] FIG. 2 is a block diagram showing the configuration of a main part of a control unit in the embodiment. [Figure 4] 10 is a flowchart showing an example of the operation of the cell picking device. [Figure 5] FIG. 4 is a diagram showing a position selection screen in the embodiment. [Figure 6] 10 is a flowchart showing another example of the operation of the cell picking device. [Figure 7] FIG. 4 is a block diagram showing another example of the configuration of the control unit in the embodiment. DETAILED DESCRIPTION OF THE INVENTION

[0011] Hereinafter, an embodiment of the present invention will be described with reference to the drawings. Fig. 1 is a front view showing a cell picking device according to this embodiment, and Fig. 2 is a schematic diagram of a microscope unit 100 included in the cell picking device. Hereinafter, left and right, front and rear, and up and down are defined by indicating that the direction of the arrowhead of the X axis in Fig. 1 is right, the direction of the arrowhead of the Y axis is backward, and the direction of the arrowhead of the Z axis is upward. Note that Fig. 2 schematically shows the microscope unit 100 as viewed from the left.

[0012] The cell picking device according to this embodiment includes a microscope unit 100, a suction unit 200, a plate exchange unit 300, a control unit 400, a display unit 500 (corresponding to the display device in the present invention), and an operation unit 600. Here, the microscope unit 100, the control unit 400, the display unit 500, and the operation unit 600 correspond to the optical microscope in the present invention. As shown in FIG. 1 , the microscope unit 100 and the plate exchange unit 300 are disposed adjacent to the left and right of the suction unit 200, respectively. However, the arrangement of the units is not limited to this, and the microscope unit 100 may be disposed to the right of the suction unit 200, and the plate exchange unit 300 may be disposed to the left of the suction unit 200.

[0013] The microscope unit 100 includes a microscope body 110 and an imaging unit 120 .

[0014] The microscope main body 110 is a so-called inverted optical microscope for observing an object from below. The microscope main body 110 includes a stage 111, a stage drive unit 112 for moving the stage 111 within an XY plane (horizontal plane), an illumination unit 115 arranged above the stage 111, an objective lens 117 arranged below the stage 111, an eyepiece lens 118 arranged diagonally above and in front of the stage 111, a light guide optical system (not shown) for bending the optical path of light that has passed through the objective lens 117 so that the light reaches the eyepiece lens 118, and an optical path branching unit 119 having a half mirror or the like arranged on the optical path of the light from the objective lens 117 to the eyepiece lens 118. The illumination unit 115 includes a light source 116 such as an LED. A region of the stage 111 arranged on the optical path of the light from the light source 116 to the objective lens 117 is made of a light-transmitting material, or the region includes an opening that allows light from the light source 116 to pass through. The stage driving unit 112 has an X-axis side driving mechanism 113 that moves the stage 111 in the left-right direction (X-axis direction), and a Y-axis side driving mechanism 114 that moves the stage 111 in the front-back direction (Y-axis direction). Both the X-axis side driving mechanism 113 and the Y-axis side driving mechanism 114 are equipped with a driving source (not shown) such as a stepping motor.

[0015] The photographing unit 120 photographs an image of the observation field of the microscope, and includes a relay lens 121 and an image sensor 122 such as a CCD sensor or a CMOS sensor.

[0016] When observing a cell 131 and photographing the observation field using the microscope unit 100, a petri dish 130 containing the cell 131 is placed on the stage 111. Light is emitted from the illumination unit 115 toward the petri dish 130. After passing through the petri dish 130 and the objective lens 117, the light is branched into two directions by the optical path branching unit 119. One of the branched light beams is guided to the eyepiece 118. This allows a user to visually observe an observation image (enlarged image) of the petri dish 130 viewed from below through the eyepiece 118. The other of the branched light beams is guided to the relay lens 121 provided in the photographing unit 120 and forms an image on the light receiving surface of the image sensor 122. This allows the photographing unit 120 to photograph an observation image similar to the above, and the obtained image is displayed on the screen of the display unit 500. Note that, although the microscope main body 110 is an inverted optical microscope here, the microscope main body 110 is not limited to this, and may be a so-called upright optical microscope in which an object is observed from above. In this case, the photographing unit 120 photographs an observation image of the Petri dish 130 viewed from above. In addition, in the above description, the illumination unit 115 is disposed above the stage 111 to illuminate the Petri dish 130 from above, but this is not limiting, and the illumination unit 115 may be disposed below the stage 111 to illuminate the Petri dish 130 from below.

[0017] The suction unit 200 includes a pipette 202 to which a pipette tip (hereinafter simply referred to as a tip) 201 can be attached, an aspirating / discharging drive unit 203 equipped with a pump or the like for aspirating and discharging cells 131 via the pipette 202, and a pipette drive unit 204 (corresponding to the collection tool drive unit in the present invention) for moving and rotating the pipette 202. The pipette drive unit 204 rotates the pipette 202 around a rotation axis 205 extending vertically, or rotates the pipette 202 in a plane perpendicular to the horizontal plane, thereby changing the attitude of the pipette 202, i.e., the inclination with respect to the vertical axis (Z-axis), and moving the pipette 202 in the axial direction of the tip 201 (corresponding to the collection tool in the present invention) attached to the pipette, and includes multiple drive mechanisms including a motor or the like (not shown). In the suction unit 200, the pipette 202 can be positioned near the plate exchange unit 300 or near the microscope unit 100 by rotating the pipette 202 around the pivot 205 using the pipette drive unit 204. The suction unit 200 may further include a tip removal mechanism (not shown) for removing the tip 201 from the tip of the pipette 202.

[0018] The plate exchange unit 300 includes a hollow base 301, a drive shaft 302 extending vertically through the upper surface of the base 301, a plate-shaped mounting unit 303 attached horizontally to the upper end of the drive shaft 302, and a mounting table drive unit 304 provided within the base 301 and equipped with a motor or the like for rotating the drive shaft 302 and moving it in the X-axis and Y-axis directions. A multiwell plate 306 having multiple wells 305 for recovering cells sampled from a Petri dish 130 and a tip rack 307 on which multiple tips 201 are set are placed on the upper surface of the mounting unit 303. In the plate exchange unit 300, the mounting table drive unit 304 rotates the drive shaft 302 to rotate the mounting unit 303, thereby allowing either the multiwell plate 306 or the tip rack 307 placed on the mounting unit 303 to be selectively positioned near the suction unit 200.

[0019] The control unit 400 controls the operations of the microscope unit 100, suction unit 200, and plate exchange unit 300, and is configured by a computer equipped with a CPU, memory, and an auxiliary storage device such as a hard disk drive or flash memory. As shown in FIG. 3 , the control unit 400 includes functional blocks such as a stage control unit 401, an imaging control unit 402, a position information acquisition unit 403, a suction unit control unit 404, a plate exchange unit control unit 405, a display control unit 406, and an evaluation value assignment unit 407. These functional blocks are realized by the CPU of the computer executing a predetermined program pre-installed in the computer. Furthermore, the control unit 400 includes a memory unit 408. The function of the memory unit 408 is realized by the auxiliary storage device provided in the computer constituting the control unit 400.

[0020] A display unit 500 for displaying images or a GUI (Graphical User Interface), etc., and an operation unit 600 for allowing the user to perform various input operations are connected to the control unit 400. The display unit 500 is configured, for example, by a liquid crystal display or an organic EL panel, and the operation unit 600 is configured, for example, by a keyboard, a pointing device such as a mouse, or a touch panel attached to the display unit 500. It is also possible to use a tablet terminal as the computer constituting the control unit 400, and use a touch panel display included in the tablet terminal as the display unit 500 and the operation unit 600.

[0021] The operation of the cell picking device according to this embodiment will be described below with reference to the flowchart of FIG.

[0022] First, the user places the tip rack 307 and the multiwell plate 306 on the placement section 303 of the plate exchange unit 300, and also places the Petri dish 130 containing cells 131 and a liquid such as a culture medium on the stage 111 of the microscope unit 100. Note that each well 305 of the multiwell plate 306 already contains a predetermined liquid such as a culture medium.

[0023] Next, the user turns on the light source 116 of the illumination unit 115, and then performs a predetermined operation on the operation unit 600 to instruct the imaging unit 120 to start imaging (Step 1). Then, under the control of the imaging control unit 402, imaging by the imaging unit 120 of the microscope unit 100 begins, and a real-time image acquired by the image sensor 122, i.e., an enlarged image of the inside of the petri dish 130, is displayed as a moving image on the screen of the display unit 500 (Step 2).

[0024] While visually observing the real-time image displayed on the display unit 500, the user performs a predetermined operation on the operation unit 600 to instruct the control unit 400 to move the petri dish 130 in the left-right direction (X-axis direction) and / or the front-back direction (Y-axis direction). As a result, under the control of the stage control unit 401, the X-axis side drive mechanism 113 and / or the Y-axis side drive mechanism 114 are driven, which moves the stage 111 accordingly, and as a result, the area within the petri dish 130 that is photographed by the photographing unit 120 changes.

[0025] The user searches for cells to be collected (cells to be collected) while visually observing the real-time image displayed on the display unit 500. When the user finds a cell (candidate cell) that is a candidate for the cell to be collected (cell to be collected), the user inputs a command to the control unit 400 to store the current stage position by performing a predetermined operation (for example, tapping on a touch panel or clicking on a mouse) via the operation unit 600 while the candidate cell is displayed on the screen of the display unit 500 (step 3).

[0026] When the control unit 400 receives the instruction, the position information acquisition unit 403 acquires position information indicating the position of the stage 111 at that time (step 4). The position information is, for example, coordinates indicating the position of the stage 111 in the XY plane. The coordinates are identified, for example, based on the drive amounts of the X-axis drive mechanism 113 and the Y-axis drive mechanism 114 used to move the stage 111 from a predetermined position (for example, an initial position) to the current position.

[0027] Next, the position information and the image displayed on the display unit 500 (that is, the observed image at the current stage position) are stored in the storage unit 408 in association with each other (step 5).

[0028] Next, the evaluation value assigning unit 407 analyzes the image (still image) stored in the memory unit 408 in step 5 to extract regions (cell regions) containing cells in the image, and determines an evaluation value (e.g., a value expressing the degree of quality of the cell in stages) for each cell (corresponding to the evaluation object in this invention) based on the pixels in each cell region, and stores the evaluation value in memory unit 408 in association with the image and position information corresponding to the image (step 6). Note that the image and the evaluation value stored in memory unit 408 in association with the position information correspond to "additional information" in this invention.

[0029] Here, the evaluation value assigning unit 407 can extract the cellular region and assign the evaluation value using, for example, a trained model based on machine learning. In this case, the trained models used include, for example, a first trained model that receives an image of an observation image taken by a microscope and outputs a cellular region in the image, and a second trained model that receives an image of the cellular region (i.e., pixels in a portion of the image of the observation field that corresponds to the cellular region) and outputs an evaluation value of the cell corresponding to the cellular region. These trained models are created in advance by machine learning and stored in the storage unit 408. Note that the first trained model can be created by machine learning using, for example, training data consisting of a large number of images containing cells and correct labels indicating the results of an expert examining each image and extracting the cellular region from the image. Furthermore, the second trained model can be created by machine learning using, for example, a large number of cell images obtained by extracting the cell region from an image of a microscope's observation field, and correct labels indicating the results of an expert looking at each cell image and assigning an evaluation value to each cell based on the contour, size, color, etc. of each cell (for example, the closer the cell contour is to a circle or ellipse, or the larger the cell, the higher the evaluation value).

[0030] Note that evaluation value assigning unit 407 may be configured to have the user assign an evaluation value, instead of assigning an evaluation value by image analysis as described above. In this case, evaluation value assigning unit 407 controls display control unit 406 to display, on the screen of display unit 500, the image stored in storage unit 408 in step 5 and a GUI for allowing the user to input an evaluation value for the cells contained in the image. When the user inputs an evaluation value via the GUI, the input evaluation value is stored in storage unit 408 in association with the image and its corresponding position information.

[0031] Thereafter, steps 3 to 6 are repeatedly executed until the user decides to end the search for candidate cells.

[0032] When the user decides to end the search for candidate cells, the user performs a predetermined operation on the operation unit 600 to input an instruction to the control unit 400 to display a position selection screen for selecting one of the position information stored in the memory unit 408 (step 7).

[0033] Upon receiving the instruction, the control unit 400 displays the position selection screen on the display unit 500 via the display control unit 406 (step 8). The position selection screen displays one or more pieces of position selection information as options selectable by the user. Each piece of position selection information corresponds to one piece of position information stored in the storage unit 408 in step 5, and includes an image captured at each stage position during the candidate cell search process, the evaluation value assigned based on the image, or both. If multiple cells are included in a single image, the position selection information may include all of the evaluation values ​​assigned to each of the multiple cells, or may include only the evaluation value of the cell with the highest evaluation. The position selection information may also include text information representing each stage position (e.g., the coordinates of the stage position).

[0034] The position selection screen may display all of the position selection information corresponding to each piece of position information stored in the storage unit 408 in the order in which the position information was stored, or may sort and display the information in descending order of the evaluation value, or may limit the position selection information to be displayed based on the evaluation value (i.e., only a predetermined number of pieces of position selection information in descending order of evaluation value are displayed on the position selection screen). Note that when a single image contains multiple cells, the sorting of the displayed images or the limiting of the images to be displayed is performed, for example, based on the evaluation value of the cell with the highest evaluation.

[0035] The user refers to the image or the evaluation value, or both, included in each piece of position selection information displayed on the display unit 500, and selects an appropriate piece of position selection information by performing a predetermined operation on the operation unit 600 (step 9). Here, the display control unit 406, the display unit 500, and the operation unit 600 correspond to the selection receiving unit in the present invention.

[0036] 5 shows an example of the position selection screen. In this example, images 701 captured at each stage position, evaluation values ​​702 assigned based on the images 701, coordinates 703 indicating the stage positions, and radio buttons 704 are displayed as position selection information 700. When the user selects an image 701, evaluation value 702, coordinates 703, or radio button 704 included in any of the position selection information 700 on this screen, for example, by clicking, the position selection information 700 including that image 701, evaluation value 702, coordinates 703, or radio button 704 is selected in step 9.

[0037] Upon receiving the selection, the control unit 400 reads out from the storage unit 408 the position information stored in association with the position selection information selected by the user. Then, based on the position information, the stage control unit 401 controls the X-axis side drive mechanism 113 and the Y-axis side drive mechanism 114 to move the stage 111 to a position corresponding to the position information (step 10). As a result, the position of the stage 111 is returned to the position corresponding to the position selection information selected in step 9, among the stage positions stored in the process of searching for the candidate cell.

[0038] Next, the user performs a predetermined operation on the operation unit 600 to designate a cell to be collected (a cell to be collected) from one or more cells included in the current observation image (real-time image) displayed on the display unit 500 (step 11). The stage control unit 401 then controls the X-axis drive mechanism 113 and the Y-axis drive mechanism 114 to move the stage 111 within the XY plane, thereby moving the cell to be collected designated in step 11 to a predetermined position (hereinafter referred to as the collection position) in the observation field. The suction unit control unit 404 then controls the pipette drive unit 204 to rotate the pipette 202 by a predetermined angle around the pivot axis 205 from a predetermined initial position and tilt the pipette 202 by a predetermined angle relative to the vertical axis. The pipette 202 is then moved along the axial direction of the tip 201 attached to the pipette 202 toward the tip of the tip 201, thereby positioning the tip of the tip 201 at the collection position. This brings the tip of the tip 201 attached to the pipette 202 into close proximity with the cells to be collected, and then the suction unit control unit 404 drives the suction / discharge drive unit 203 to suction the cells to be collected into the tip 201 (step 12).

[0039] After the cells to be collected have been aspirated into the tip 201 as described above, the pipette 202 is moved along the axial direction of the tip 201 toward the base end of the tip 201 under the control of the suction unit control unit 404, thereby lifting the tip 201 from the Petri dish 130. Next, the pipette 202 is rotated to an upright position (a position in which the tip of the tip 201 faces directly downward), and the pipette 202 is rotated about the pivot shaft 205, thereby positioning the pipette 202 and the tip 201 above the mounting portion 303 of the plate exchange unit 300. Then, under the control of the plate exchange unit control unit 405, the mounting portion 303 is moved and rotated in a horizontal plane, thereby positioning a predetermined well 305 of a multiwell plate 306 mounted on the mounting portion 303 directly below the pipette 202. Thereafter, the pipette 202 is moved toward the tip of the chip 201 (i.e., downward), thereby bringing the tip of the chip 201 closer to the well 305, and the suction / discharge drive unit 203 is driven to discharge the cells to be collected in the chip 201 into the well 305 (step 13).

[0040] As described above, the cell picking device according to this embodiment makes it easy to search for a suitable cell to be collected by moving the stage 111 provided on the microscope unit 110 in the XY plane, and then return the stage 111 to the position where the most suitable cell was observed and collect that cell.

[0041] In the above example, when searching for the candidate cells, the stage 111 of the microscope unit 100 is moved appropriately based on instructions from the user, but instead, automatic scanning of the stage 111 may be performed. In this case, an example of the operation of the cell picking device according to this embodiment will be described below with reference to the flowchart in FIG.

[0042] First, the user performs a predetermined operation on the operation unit 600 to instruct the microscope unit 100 to start automatic scanning (step 21). As a result, under the control of the imaging control unit 402, imaging by the imaging unit 120 begins (step 22).

[0043] Next, the stage control unit 401 sets a variable N, which represents the stage position on the XY plane, to 1 (step 23), and controls the X-axis side driving mechanism 113 and the Y-axis side driving mechanism 114 to move the stage 111 to a predetermined first stage position (step 24).

[0044] Next, the position information acquisition unit 403 acquires position information representing the current position of the stage 111 from the storage unit 408 (step 25). Note that the position information (i.e., XY coordinates) of each stage position in automatic scanning is set in advance and stored in the storage unit 408.

[0045] Next, the position information indicating the current stage position and the image (still image) acquired by the imaging unit 120 at the current stage position are stored in the storage unit 408 in association with each other (step 26).

[0046] Next, the stage control unit 401 determines whether the movement of the stage 111 to all predetermined stage positions has been completed (step 27), and if it determines that the movement has not been completed, it increments the variable N (step 28) and moves the stage 111 to the Nth stage position (step 24). Then, steps 24 to 28 are repeatedly executed until it is determined in step 27 that the movement to all stage positions has been completed.

[0047] Thereafter, when it is determined in step 27 that movement to all stage positions has been completed, the evaluation value assigning unit 407 then analyzes the images stored in the storage unit 408, i.e., the images (still images) acquired at each stage position during the automatic scanning, to extract cellular regions in each image and assign an evaluation value to each cell based on the pixels of each cellular region (step 29). Note that the methods of extracting cellular regions and assigning evaluation values ​​are the same as those in step 6 above, and therefore will not be described in detail.

[0048] Next, the user performs a predetermined operation on the operation unit 600, thereby inputting an instruction to the control unit 400 to display a position selection screen for selecting one of the stage positions in the above-mentioned automatic scanning (step 30).

[0049] Upon receiving the instruction, the control unit 400 causes the display control unit 406 to display the location selection screen on the screen of the display unit 500 (step 31). The location selection screen displays one or more pieces of location selection information as options selectable by the user. This location selection information is the same as that displayed in step 8 described above, and therefore a detailed description thereof will be omitted.

[0050] The position selection screen may display all N pieces of position selection information corresponding to the N stage positions in the automatic scanning, or may display only the position selection information corresponding to the stage positions among the N stage positions where a cell was captured in the image acquired at that position (i.e., where a cell region was extracted in step 6). Furthermore, the position selection information may be sorted and displayed in descending order of the evaluation value assigned to the cells in the image, or only a predetermined number of pieces of position selection information in descending order of the evaluation value assigned to the cells in the image may be displayed on the position selection screen.

[0051] The user refers to the image or the evaluation value, or both, included in each piece of position selection information, and performs a predetermined operation on the operation unit 600 to select an appropriate piece of position selection information (step 32).

[0052] Then, the position information stored in association with the position selection information selected by the user is read from the storage unit 408. Then, based on the position information, the stage control unit 401 controls the X-axis side drive mechanism 113 and the Y-axis side drive mechanism 114 to move the stage 111 to a position corresponding to the position information (step 33).

[0053] Next, the user performs a predetermined operation on the operation unit 600 to specify a cell to be collected (cell to be collected) from one or more cells included in the real-time image of the current observation image displayed on the display unit 500 (step 34). Thereafter, similar to steps 12 and 13 described above, the cell to be collected is aspirated from the dish 130 into the chip 201 (step 35), and the cell to be collected is discharged into a pre-specified well 305 of the multiwell plate 306 (step 36).

[0054] In addition, the cell picking device of this embodiment may be equipped with a function to, in step 10 or step 33, move the stage 111 to a stage position (hereinafter referred to as the selected position) corresponding to the position selection information selected by the user, and then compare images (hereinafter referred to as past images) stored in the memory unit 407 that were acquired at the selected position during the search process for the candidate cell or the automatic scanning process with a real-time image of the current observation image, and adjust the position of the stage 111 so that the difference between the two is reduced.

[0055] An example configuration of the control unit 1400 in this case is shown in Fig. 7. In this figure, components that are the same as or correspond to those shown in Fig. 3 are assigned reference numerals with the same last three digits, and their explanations will be omitted as appropriate. In this example configuration, the control unit 1400 includes an image comparison unit 1409 and a movement amount calculation unit 1410 in addition to the same functional blocks and memory unit 1408 as those shown in Fig. 3. Here, the image comparison unit 1409, the movement amount calculation unit 1410, and the stage control unit 1401 correspond to the stage position adjustment unit in this invention.

[0056] When the cell picking device according to this embodiment is configured to include such a control unit 1400, after the stage 111 is moved to the selected position by executing step 10 or step 33 described above, the image comparison unit 1409 reads out from the storage unit 1408 the past image stored in step 5 or step 26 for the selected position and compares the past image with the current observation image (hereinafter referred to as the current image) acquired from the image sensor 122. If the comparison reveals a difference between the two that exceeds a predetermined allowable amount, the movement amount calculation unit 1410 calculates the amount of movement of the stage 111 that compensates for the difference. Specifically, for example, for one of the cells included in the past image (e.g., the cell with the highest evaluation value), the coordinates of the cell in the past image and the coordinates of the cell in the current image are identified, and the difference between the two coordinates is calculated. Then, based on the difference and the magnification of the microscope unit 100, the drive amounts of the X-axis drive mechanism 113 and the Y-axis drive mechanism 114 required to match the position of the cell in the current observation field with the position of the cell in the past image are calculated. Thereafter, the stage control unit 1401 controls the X-axis drive mechanism 113 and the Y-axis drive mechanism 114 so as to move the stage 111 by the movement amount calculated by the movement amount calculation unit 1410.

[0057] By doing this, even if the position of cell 131 in dish 130 has changed slightly due to movement of stage 111 between the time the previous image was taken and the completion of step 10 or step 33, the position of cell 131 in the current observation field can be made closer to the state when the previous image was taken.

[0058] Although specific examples of the form for carrying out the present invention have been described above, the present invention is not limited to the above-described embodiments, and appropriate modifications are permitted within the scope of the spirit of the present invention.

[0059] For example, the cell picking device according to the embodiment may be provided with a function for fine-tuning the position of the stage 111 so that an object designated by the user in the previous image is located at a predetermined position within the current observation field. In this case, in step 9 or step 32, after the control unit 400 receives the user's selection of position selection information (i.e., the selection of the stage position to which the user wishes to return), the display control unit 406 reads out the previous image stored in the memory unit 408, which corresponds to the stage position selected by the user. The previous image is then displayed on the screen of the display unit 500, and the user is prompted to select any object (e.g., a cell to be collected) in the previous image via the operation unit 600 (here, the display control unit 406, the display unit 500, and the operation unit 600 correspond to the object designation receiving unit in the present invention). The control unit 400 then analyzes the previous image to identify the contour of the object. Then, after the movement of the stage 111 in step 10 or step 33, the control unit 400 identifies the position of the target within the current observation field of view based on the contour, and identifies the drive amounts of the X-axis side drive mechanism 113 and the Y-axis side drive mechanism 114 required to move the target to a predetermined position within the observation field of view (for example, the center of the field of view or the above-mentioned collection position). Thereafter, the stage drive unit 112 adjusts the position of the stage 111 by driving the X-axis side drive mechanism 113 and the Y-axis side drive mechanism 114 by the drive amounts. This saves the user the trouble of moving the target to the center of the observation field of view, for example, after execution of step 9 or step 32.

[0060] Furthermore, in the above embodiment, the control units 400, 1400 have evaluation value assigning units 407, 1407 (corresponding to the evaluation value determining unit in the present invention), but the picking device according to the present invention does not necessarily have to have an evaluation value determining unit. In that case, step 6 in the flowchart of FIG. 4 or step 29 in the flowchart of FIG. 6 is omitted. Furthermore, the above-mentioned position selection information does not include the evaluation value.

[0061] Furthermore, the present invention is not limited to the cell picking device described above, but can be widely applied to any picking device that has an optical microscope and picks particulate objects, such as spores, pollen, or seeds, as collection targets. In the above embodiment, the collection target in a liquid contained in a container (specifically, cells 131 in a culture medium contained in a Petri dish 130) is sucked into the tip 201 and collected. However, the picking device according to the present invention is not limited to a configuration that uses a tubular collection tool such as the tip 201 as a collection tool for collecting the collection target. For example, the collection target (e.g., a cell colony) present on a solid (e.g., an agar medium) contained in the Petri dish 130 may be scraped off with a rod-shaped collection tool such as a platinum loop, thereby attaching the collection target to the tip of the collection tool.

[0062] Furthermore, the present invention is not limited to the picking device, but can also be applied to a standalone optical microscope that does not have the function of picking up particulate objects.

[0063] [Aspect] It will be apparent to those skilled in the art that the above-described exemplary embodiments are examples of the following aspects.

[0064] (Item 1) An optical microscope according to one aspect of the present invention comprises: An objective lens, a stage on which an object is placed; a stage driving unit that moves the stage within a plane perpendicular to the optical axis of the objective lens; an imaging unit that images the object through the objective lens; a storage unit that stores a position of the stage at a predetermined timing in association with additional information based on an image captured by the imaging unit at the predetermined timing; a display control unit that causes a display device to display position selection information including the additional information; a selection receiving unit that receives an operation to select the position selection information displayed on the display device; a stage control unit that controls the stage driving unit to move the stage to the selected position, which is the position stored in the storage unit in association with the additional information included in the position selection information selected via the selection receiving unit; It has the following characteristics.

[0065] (2) The optical microscope according to paragraph 2 is the optical microscope according to paragraph 1, The additional information is an evaluation value for an evaluation object included in the image.

[0066] (3) The optical microscope according to paragraph 3 is the optical microscope according to paragraph 1 or 2, The additional information is the image itself.

[0067] (4) The optical microscope according to paragraph 4 is the optical microscope according to paragraph 3. Furthermore, a stage position adjusting unit that, after the stage has moved to the selected position, compares a real-time image captured by the imaging unit at the current stage position with the image stored in the storage unit in association with the selected position, and controls the stage driving unit to match the two images; It has the following characteristics.

[0068] (5) The optical microscope according to paragraph 5 is the optical microscope according to paragraph 3. Furthermore, an object designation receiving unit that allows a user to select an arbitrary object in the image stored in the storage unit in association with the selection position; The stage control unit further The stage driving unit is controlled so that the object selected by the object designation receiving unit is positioned at a predetermined position within the observation field of view.

[0069] (Item 6) The optical microscope according to item 6 is the optical microscope according to item 2, an evaluation value determination unit that determines the evaluation value by analyzing the image; It further has the following.

[0070] (Item 7) The optical microscope according to item 7 is the optical microscope according to any one of items 1 to 6, further comprising: a control unit that controls the stage driving unit and the imaging unit so as to perform an automatic scan by moving the stage at predetermined intervals within the plane while imaging by the imaging unit; The memory unit stores the position of each stage during the automatic scanning as the position of the stage at the specified timing, and stores, as the additional information, information based on images captured by the photographing unit at each stage position during the automatic scanning.

[0071] (Item 8) The picking device according to item 8 is An optical microscope according to any one of items 1 to 7; a sampling tool for sampling an object to be sampled that is located within the observation field of the microscope; a sampling tool driving unit that drives the sampling tool; It has the following characteristics. [Explanation of symbols]

[0072] 100...Microscope unit 110...Microscope 111...Stage 112...Stage drive unit 113...X-axis drive mechanism 114...Y-axis drive mechanism 115...Lighting department 117...Objective lens 120...Photography department 130…Petri dish 131...cell 200...Suction unit 201...Chips 202...Pipette 203...Suction and discharge drive unit 204...Pipette drive unit 300...Plate exchange unit 305...Well 306...Multiwell plate 400...Control unit 401...Stage control section 402...imaging control unit 403...Location information acquisition unit 404...Suction unit control section 405...Plate exchange unit control section 406...Display control unit 407...Evaluation value assignment unit 408...Storage section 500...Display section 600...Operation unit

Claims

1. An objective lens, a stage on which an object is placed; a stage driving unit that moves the stage within a plane perpendicular to the optical axis of the objective lens; an imaging unit that images the object through the objective lens; a storage unit that stores a position of the stage at a predetermined timing in association with additional information based on an image captured by the imaging unit at the predetermined timing; a display control unit that causes a display device to display position selection information including the additional information; a selection receiving unit that receives an operation to select the position selection information displayed on the display device; a stage control unit that controls the stage driving unit to move the stage to the selected position, which is the position stored in the storage unit in association with the additional information included in the position selection information selected via the selection receiving unit; An optical microscope with

2. The optical microscope according to claim 1 , wherein the additional information is an evaluation value for an evaluation object included in the image.

3. The optical microscope according to claim 1 , wherein the additional information is the image itself.

4. Furthermore, a stage position adjusting unit that, after the stage has moved to the selected position, compares a real-time image captured by the imaging unit at the current stage position with the image stored in the storage unit in association with the selected position, and controls the stage driving unit to match the two images; 4. The optical microscope according to claim 3, further comprising:

5. Furthermore, an object designation receiving unit that allows a user to select an arbitrary object in the image stored in the storage unit in association with the selection position; The stage control unit further controlling the stage driving unit so that the object selected by the object designation receiving unit is positioned at a predetermined position within the observation field of view; The optical microscope according to claim 3 .

6. Furthermore, an evaluation value determination unit that determines the evaluation value by analyzing the image; 3. The optical microscope according to claim 2, further comprising:

7. Furthermore, a control unit that controls the stage driving unit and the imaging unit so as to perform an automatic scan by moving the stage at predetermined intervals within the plane while imaging by the imaging unit; The optical microscope according to claim 1, wherein the memory unit stores the position of each stage during the automatic scanning as the position of the stage at the specified timing, and stores, as the additional information, information based on images captured by the photographing unit at each stage position during the automatic scanning.

8. An optical microscope according to any one of claims 1 to 7; a sampling tool for sampling an object to be sampled that is located within the observation field of the microscope; a sampling tool driving unit that drives the sampling tool; A picking device having the above structure.

Images