JPWO2019088030A1 - Shooting control device, operation method of shooting control device, and shooting control program - Google Patents

Abstract

In the imaging control device, the operation method of the imaging control device, and the imaging control program, deterioration of the image quality of the captured image due to an error in the container is suppressed. When the shape information of the bottom surface of the container in which the observation target is housed is different from the shape information of the bottom surface of the container determined in advance, the notification unit (display device 30 as an example) is notified in advance that the information is different. The imaging condition 16 is changed from the imaging condition based on the shape information of the bottom surface of the predetermined container to the imaging condition based on the shape information of the bottom surface of the container in which the observation target is housed.

Description

The present invention relates to an image pickup control device and an operation method of the image pickup control device for causing an image pickup unit to image an observation object housed in a container, and a shooting control program.

Pluripotent stem cells such as ES (Embryonic Stem) cells and iPS (Induced Pluripotent Stem) cells have the ability to differentiate into cells of various tissues, such as regenerative medicine, drug development, and elucidation of diseases. It is attracting attention as something that can be applied in.

Then, a method has been proposed in which pluripotent stem cells such as ES cells and iPS cells, or cells in which differentiation has been induced are imaged with a microscope or the like, and the differentiation state of the cells is evaluated by capturing the characteristics of the images. There is.

Generally, when the cells are photographed using a microscope device, the imaging conditions are set in advance, and the imaging is performed under the set imaging conditions. However, in the container containing the cultured pluripotent stem cells, cloudiness of the container, that is, droplets adhering to the container, changes in the amount and concentration of the culture solution due to evaporation, etc., incorrect container type, human error, etc. The shooting conditions set above may not always be the optimum conditions at the time of shooting due to various factors.

Therefore, in Patent Document 1, a pre-photograph is performed to acquire a pre-captured image, and the light amount distribution of the irradiation light is set so that the lower the brightness of the pre-captured image, the larger the incident light amount, and the image is photographed again (main shooting). ), A technique for reducing image density unevenness caused by irradiation light is disclosed.

Japanese Unexamined Patent Publication No. 2013-228361

Usually, pluripotent stem cells such as ES cells and iPS cells are housed in a culture vessel such as a well plate and cultured in an incubator in a state where the environmental temperature and humidity are controlled. Then, when imaging the cultured pluripotent stem cells, the culture vessel is moved from the incubator to the microscope device.

However, in the culture vessel used for microscopic observation, the surface treatment of the inner surface of the culture vessel, the material of the vessel, and the like may differ depending on the type of the culture vessel, for example, the difference in the manufacturer. If the surface treatment and the material of the container are different, the culture state of the observation target housed in the culture container and the shape of the meniscus formed on the surface of the liquid will be different, and the imaging conditions such as optical conditions will be different. May change. Further, in general, most of the culture containers are disposable type, and the manufacturing accuracy is not so good. The deflection (unevenness) formed on the bottom surface of the culture container also differs depending on the type of culture container, such as a difference in the manufacturer, and the range of manufacturing error may also differ.

On the other hand, as described above, when photographing cells with a microscope device, it has been proposed to perform so-called tiling imaging in order to acquire a high-magnification wide-field image. Specifically, by moving the stage on which the culture vessel is installed relative to the imaging optical system, each observation position in the culture vessel is scanned, an image of each observation position is taken, and then the image is taken. A method of combining images for each observation position has been proposed.

Here, since the bottom surface of the culture vessel has deflection, the drive unit moves the objective lens in the optical axis direction for each observation position based on the deflection information of the bottom surface of the culture vessel to perform autofocus control and focus. It needs to be aligned. However, the deflection formed on the bottom surface of the culture vessel differs depending on the type of the culture vessel, for example, the manufacturer differs. Therefore, when the imaging conditions of the microscope device are set in a predetermined type of culture container installed in the microscope device, that is, the culture container intended by the user, a culture container other than the culture container intended by the user becomes the microscope device. When installed, the deflection of the bottom surface of the culture vessel, that is, the height of the bottom surface of the culture vessel, rather than the movable range in which the drive unit moves the objective lens in the optical axis direction (hereinafter referred to as the driveable range by the drive unit). The difference may become large, and as a result, the focal position may not be aligned due to exceeding the driveable range by the drive unit, and the captured image may become a blurred image. If the captured image becomes a blurred image, it is necessary to change the culture vessel to the culture vessel intended by the user and start over from the observation target, that is, the culture of cells.

The present invention has been made in view of the above circumstances, and an object of the present invention is to provide a photographing control device, an operation method of the photographing control device, and a photographing control program capable of suppressing deterioration of the image quality of the photographed image due to an error in the container. ..

When the shape information of the bottom surface of the container in which the observation target is housed is different from the shape information of the bottom surface of the container, the photographing control device of the present invention notifies the notification unit that the shape information is different. It is provided with a control unit that causes the imaging unit to take an image by changing the imaging conditions based on the shape information of the bottom surface of the container predetermined to the imaging conditions based on the shape information of the bottom surface of the container in which the observation target is housed.

In the present invention, the "bottom surface of the container" is the bottom surface of the container that houses the observation target, and means the installation surface of the observation target.

Further, in the present invention, the "notifying unit" includes a display for visually displaying a message or the like, an audio reproduction device for displaying an audible display by outputting voice, a printer for recording on a recording medium such as paper, and a printer for permanently visible display. It means a communication means such as a telephone and an indicator light, and at least two or more of the display, the voice reproduction device, the printer, the communication means, and the display light may be combined.

Further, in the present invention, the "shape information of the bottom surface of the container" includes at least one of the height of the bottom surface of the container, the thickness of the bottom surface of the container, and the curvature of the bottom surface of the container.

In the present invention, the "height of the bottom surface of the container" means the distance from the predetermined reference plane to the bottom surface of the container. Here, the reference surface may be the lower surface of the bottom portion of the container, or may be a surface including the light irradiation port of the measurement unit and orthogonal to the vertical direction of the container, and may be appropriately determined. When the reference surface is the lower surface of the bottom of the container, the "height of the bottom of the container" coincides with the "thickness of the bottom of the container".

Further, in the present invention, the "container" is collectively referred to as a container including the lid when the lid is covered.

Further, in the imaging control device of the present invention, the control unit observes by causing the measuring unit to perform pre-measurement for measuring the shape of the bottom surface of the container in which the observation target is housed before the main imaging by the imaging unit. The shape information of the bottom surface of the container in which the object is housed may be acquired.

In the present invention, the "main shooting" means a shooting performed when the user obtains a desired shot image, and the "pre-measurement" means a pre-measurement performed before the main shooting is performed.

Further, in the photographing control device of the present invention, the control unit irradiates the measurement unit with light on the bottom surface of the container in which the observation target is housed, and based on the reflected light reflected on the bottom surface, the bottom surface of the container is subjected to shape information. You may get the height.

In this case, the measuring unit may be a laser displacement sensor.

Further, in the photographing control device of the present invention, the measuring unit has an imaging unit.
The control unit may acquire the curvature of the bottom surface of the container as shape information based on the captured image acquired by having the imaging unit image the observation object housed in the container.

Further, the imaging control device of the present invention moves the container containing the observation target relative to the imaging optical system that forms an image of the observation target in the container in the optical axis direction of the imaging optical system. The control unit controls the container when the height difference of the bottom surface of the container containing the observation target is larger than the size of the movable range in which the optical axis driving unit moves the imaging optical system or the container relative to the optical axis. The position of the above range may be changed with respect to the optical axis direction drive unit according to the height of the bottom surface of the image, and the image pickup unit may be allowed to take an image.

In the present invention, "a movable range in which the optical axis direction driving unit moves the imaging optical system or the container relative to the optical axis direction" means a range in which the optical axis direction driving unit can drive in the optical axis direction. To do. Further, the "height difference of the bottom surface of the container" means the difference between the lowest point and the highest point on the entire bottom surface of the container.

Further, the photographing control device of the present invention includes a shape information storage unit that stores shape information of the container.
The shape information storage unit may store a table in which the identification information of the container in which the observation target is housed and the shape information of the bottom surface of the container are associated with each other.

Further, in the imaging control device of the present invention, the container may be a dish, a well plate or a flask.

The method of operating the imaging control device of the present invention is a method of operating the imaging control device including the control unit.
When the shape information of the bottom surface of the container in which the observation target is housed is different from the shape information of the bottom surface of the container, the control unit notifies the notification unit that the shape information is different, or is predetermined. The imaging condition is changed from the imaging condition based on the shape information of the bottom surface of the container to the imaging condition based on the shape information of the bottom surface of the container in which the observation target is housed, and the imaging unit is made to photograph.

It should be noted that it may be provided as a program for causing a computer to execute the operation method of the photographing control device according to the present invention.

The other imaging control device according to the present invention has a memory for storing instructions to be executed by the computer, and
The processor comprises a processor configured to execute a stored instruction.
When the shape information of the bottom surface of the container in which the observation target is housed is different from the shape information of the bottom surface of the predetermined container, the notification unit is notified that the information is different, or the shape information of the bottom surface of the predetermined container is different. A process of changing the imaging condition based on the shape information to the imaging condition based on the shape information of the bottom surface of the container in which the observation target is housed and causing the imaging unit to perform imaging is executed.

According to the present invention, when the shape information of the bottom surface of the container in which the observation target is housed is different from the shape information of the bottom surface of the container determined in advance, the notification unit is notified that the shape information is different, or is determined in advance. Since the imaging condition is changed from the imaging condition based on the shape information of the bottom surface of the container to the imaging condition based on the shape information of the bottom surface of the container containing the observation target, the imaging unit is made to take an image. In the case of notifying, the user can know that the container in which the observation target to be photographed is housed is not the container desired by the user, that is, the predetermined container, so that the imaging target is, for example, a predetermined container. It is possible to take measures such as replacing the observation target with the observation target housed in the container or re-culturing the observation target in a predetermined container. Therefore, since it is possible to prevent the control unit from causing the image pickup unit to take a photographed image having a deteriorated image quality, it is possible to suppress the deterioration of the image quality of the photographed image due to an error in the container. In addition, when changing the imaging conditions based on the shape information of the bottom surface of the container containing the observation target and causing the imaging unit to take an image, the imaging unit takes an image suitable for the shape of the bottom surface of the container containing the observation object. Shooting can be performed under the conditions, and deterioration of the image quality of the shot image due to a mistake in the container can be suppressed.

The figure which shows the schematic structure of the microscope apparatus of 1st Embodiment in the microscope observation system of this embodiment. Schematic diagram showing the configuration of the imaging optical system Schematic diagram showing the configuration of the imaging optical system drive unit Perspective view showing the configuration of the stage Block diagram showing the configuration of the microscope observation system of this embodiment Schematic diagram showing a culture vessel containing an observation target Diagram for explaining shape information of the bottom surface of the culture vessel Flow chart of a series of processes performed in the microscope observation system of the first embodiment Flow chart of imaging condition change processing performed in the microscope observation system of the first embodiment Flow chart of a series of processes performed in the microscope observation system of the second embodiment Flow chart of imaging condition change processing performed in the microscope observation system of the second embodiment Flow chart of a series of processes performed in the microscope observation system of the third embodiment Flow chart of a series of processes performed in the microscope observation system of the fourth embodiment Flow chart of a series of processes performed in the microscope observation system of the fifth embodiment Flow chart of a series of processes performed in the microscope observation system of the sixth embodiment Block diagram showing the configuration of the microscope observation system of the seventh embodiment A conceptual diagram showing an example of a mode in which the imaging control program is installed in the microscope control device from the storage medium in which the imaging control program according to the first to third embodiments is stored.

Hereinafter, the microscope observation system 1 using the first embodiment of the imaging control device of the present invention will be described in detail with reference to the drawings. FIG. 1 is a diagram showing a schematic configuration of a microscope device 10 in the microscope observation system 1 of the first embodiment. In the present embodiment, the microscope observation system 1 is composed of a microscope device 10 and a microscope control device 20 described later, and the microscope control device 20 is an example of the imaging control device of the present invention.

The microscope device 10 captures a phase-difference image of the cultured cells to be observed. Specifically, as shown in FIG. 1, the microscope device 10 includes a white light source 11, a condenser lens 12, a slit plate 13, an imaging optical system 14, an imaging optical system driving unit 15, and an imaging unit that emit white light. 16. The detection unit 18 and the stage 51 are provided.

The slit plate 13 is provided with a ring-shaped slit that transmits white light to a light-shielding plate that blocks white light emitted from the white light source 11, and is ring-shaped as the white light passes through the slit. Illumination light L is formed.

FIG. 2 is a diagram showing a detailed configuration of the imaging optical system 14. As shown in FIG. 2, the imaging optical system 14 includes a retardation lens 14a and an imaging lens 14d. The phase difference lens 14a includes an objective lens 14b and a phase plate 14c. The phase plate 14c has a phase ring formed on a transparent plate that is transparent to the wavelength of the illumination light L. The size of the slit of the slit plate 13 described above has a conjugate relationship with the phase ring of the phase plate 14c.

The phase ring is formed by forming a ring-shaped phase film that shifts the phase of the incident light by 1/4 wavelength and a dimming filter that dims the incident light. The direct light incident on the phase ring is shifted in phase by 1/4 wavelength and its brightness is weakened by passing through the phase ring. On the other hand, most of the diffracted light diffracted by the observation target passes through the transparent plate of the phase plate 14c, and its phase and brightness do not change.

The objective lens 14b is moved in the optical axis direction of the objective lens 14b by the imaging optical system drive unit 15 described later. In the present embodiment, the optical axis direction and the Z direction (vertical direction) of the objective lens 14b are the same directions. Autofocus control is performed by moving the objective lens 14b in the Z direction, and the contrast of the phase difference image captured by the imaging unit 16 is adjusted.

Further, the magnification of the retardation lens 14a may be changed. Specifically, the retardation lens 14a or the imaging optical system 14 having different magnifications may be interchangeably configured. The phase difference lens 14a or the imaging optical system 14 may be replaced automatically or manually by the user.

Here, FIG. 3 shows a schematic diagram showing the configuration of the imaging optical system drive unit 15. The imaging optical system driving unit 15 makes the culture container 50 in which the observation target S is housed the light of the imaging optical system 14 with respect to the imaging optical system 14 that forms an image of the observation target S in the culture container 50. It is relatively moved in the axial direction, and is an example of the optical axis direction driving unit of the present invention.

As shown in FIG. 3, the imaging optical system drive unit 15 of the present embodiment includes an actuator 15B and a piezoelectric element 15A arranged on the upper side of the actuator 15B in the vertical direction. The actuator 15B includes a moving member that moves in the vertical direction (Z direction) and a pulse motor that transmits power to the moving member, and drives the actuator 15B based on a control signal output from a control unit 22 described later. The actuator 15B moves the piezoelectric element 15A in the vertical direction by moving the moving member.

The piezoelectric element 15A is driven based on a control signal output from the control unit 22 described later, and moves the objective lens 14b in the vertical direction. The imaging optical system drive unit 15 is configured to pass the retardation image that has passed through the retardation lens 14a as it is.

In the present embodiment, the piezoelectric element 15A can move the imaging optical system 14 in the Z direction at a higher speed than the actuator 15B. On the other hand, the piezoelectric element 15A has a smaller driveable range in the vertical direction than the actuator 15B. Specifically, the driveable range of the piezoelectric element 15A is, for example, 640 μm, while the driveable range of the actuator B is, for example, 5 mm. Here, the value of the driveable range of the piezoelectric element 15A is stored in advance in the secondary storage unit 25 described later. When the value in the driveable range of the piezoelectric element 15A is not stored in the secondary storage unit 25, the user can input the value in the above range by the input device 40.

In the imaging optical system drive unit 15 of the present embodiment, the piezoelectric element 15A is used for the movement of the objective lens 14b in the Z direction when autofocus control is performed, and the movement of the objective lens 14b in the Z direction is the piezoelectric element. When it deviates from the driveable range of 15A, the position of the driveable range of the piezoelectric element 15A is changed by moving the piezoelectric element 15A in the Z direction by the actuator 15B, and the Z of the objective lens 14b is changed by the piezoelectric element 15A. Allows movement in the direction. The driving method of the piezoelectric element 15A and the actuator 15B will be described in detail later.

The imaging optical system drive unit 15 of the present embodiment is composed of the piezoelectric element 15A and the actuator 15B, but the present invention is not limited to this, and the objective lens 14b can be moved in the Z direction. Any other known configuration can be used. Further, although the actuator 15B of the present embodiment has a pulse motor, the present invention is not limited to this, as long as the piezoelectric element 15A can be moved in the Z direction, and other known configurations may be used. Can be used.

Further, the imaging optical system driving unit 15 of the present embodiment moves only the objective lens 14b in the Z direction, but the present invention is not limited to this, and the retardation lens 14a is moved in the Z direction. It may be configured to be made to.

The imaging lens 14d receives a retardation image that has passed through the retardation lens 14a and the imaging optical system driving unit 15, and forms an image on the imaging unit 16.

The image pickup unit 16 includes an image pickup device that receives an image of the observation target S imaged by the imaging lens 14d, images the observation target S, and outputs a phase difference image as an observation image. As the image pickup device, a CCD (charge-coupled device) image sensor, a CMOS (Complementary Metal-Oxide Semiconductor) image sensor, or the like can be used. As the image sensor, an image sensor provided with an RGB (Red Green Blue) color filter may be used, or a monochrome image sensor may be used.

The detection unit 18 detects the position of the bottom surface 50a of the culture vessel 50 installed on the stage 51 in the Z direction (vertical direction). Specifically, the detection unit 18 includes a first displacement sensor 18a and a second displacement sensor 18b. The first displacement sensor 18a and the second displacement sensor 18b are provided side by side in the X direction shown in FIG. 1 with the retardation lens 14a interposed therebetween. The first displacement sensor 18a and the second displacement sensor 18b in the present embodiment are laser displacement meters (laser displacement sensors), and the culture vessel 50 is irradiated with laser light and the reflected light is detected to detect the reflected light in the culture vessel. The position of the bottom surface 50a of the 50 in the Z direction is detected. Here, FIG. 6 shows a schematic view showing the culture vessel 50 in which the observation target is housed. The bottom surface 50a of the culture container 50 is the bottom surface 50a in the culture container 50 that houses the observation target S, and is the installation surface of the observation target S. This installation surface is the boundary surface between the bottom of the culture vessel 50 and the cells to be observed. Further, the lower surface of the bottom of the culture container 50 is the lower surface 50b.

In the present embodiment, the detection unit 18 is an example of the measurement unit of the present invention in which the pre-measurement is performed. The detection unit 18 performs pre-measurement based on the control signal output from the control unit 22 described later. Specifically, by irradiating the bottom surface 50a of the culture vessel 50 with laser light and detecting the reflected light reflected by the bottom surface 50a of the culture vessel 50, the shape information of the bottom surface 50a of the culture vessel 50 can be used as the shape information of the culture vessel 50. The height of the bottom surface 50a is detected. In the present embodiment, the height of the bottom surface 50a of the culture container 50 is set with the detection unit 18 as a reference plane, and the value of the signal of the reflected light detected by the detection unit 18 is a value representing the height of the bottom surface 50a of the culture container 50. .. The detection unit 18 measures the height of the entire bottom surface 50a of the culture vessel 50 with a spatial resolution of 10 μm × 10 μm in the XY directions. As for the spatial resolution, it is preferable to use the spatial resolution used at the time of measuring the shape information 29 stored in the secondary storage unit 25 described later.

In the present embodiment, the height value of the bottom surface 50a of the culture vessel 50 is the value of the signal of the reflected light detected by the detection unit 18, but the present invention is not limited to this, and the value of the reflected light is not limited to this. The value obtained by converting the signal value into a distance, that is, the distance from the detection unit 18 to the bottom surface 50a of the culture container 50 may be the height of the bottom surface 50a of the culture container 50. Further, the detection unit 18 further detects the reflected light reflected by the lower surface 50b (see FIG. 6) of the bottom surface of the culture container 50, so that the value of the signal of the reflected light reflected by the bottom surface 50a of the culture container 50 is used to determine the culture container 50. The value of the reflected light reflected by the lower surface 50b of the bottom portion may be subtracted to calculate a value representing the thickness of the bottom portion of the culture vessel 50, and this value may be used as a value representing the height of the bottom surface 50a of the culture vessel 50. Further, the value representing this height may be converted into the value of the actual distance and used.

Although the measuring unit 18 of the present embodiment is used, the present invention is not limited to this. For example, a laser displacement sensor may be provided in the microscope device 10 separately from the detecting unit 18. As the laser displacement sensor, a specular optical system measuring instrument can be used. The present invention is not limited to the laser displacement sensor, and for example, a confocal sensor can also be used.

The position information indicating the position of the bottom surface 50a of the culture vessel 50 in the Z direction detected by the detection unit 18 is output to the control unit 22, and the control unit 22 drives the imaging optical system based on the input position information. The unit 15 is controlled to perform autofocus control.

A stage 51 is provided between the slit plate 13, the retardation lens 14a, and the detection unit 18. A culture vessel 50 containing cells to be observed is installed on the stage 51.

As the culture vessel 50, a petri dish, a dish, a well plate in which a plurality of wells are arranged, or the like can be used. In this embodiment, a well plate in which a plurality of wells are arranged is used as a culture container. However, although the culture vessel 50 described above is an example of one well in the well plate in the present embodiment, the well plate will be collectively referred to as the culture vessel 50 below. The cells contained in the culture vessel 50 include pluripotent stem cells such as iPS cells and ES cells, nerve, skin, myocardial and liver cells induced to differentiate from the stem cells, and skin and retina extracted from the human body. There are cells of myocardium, blood cells, nerves and organs.

The stage 51 is moved in the X and Y directions orthogonal to each other by the horizontal drive unit 17 (see FIG. 5) described later. The X direction and the Y direction are directions orthogonal to each other on a plane parallel to the observation target installation surface P1, and the Z direction is a direction orthogonal to the X direction and the Y direction.

FIG. 4 is a diagram showing an example of the stage 51. A rectangular opening 5 in the center of the stage 51
1a is formed. The culture vessel 50 is installed on the member forming the opening 51a, and the phase difference image of the cells in the culture vessel 50 is configured to pass through the opening 51a.

Next, the configuration of the microscope control device 20 that controls the microscope device 10 will be described. FIG. 5 is a block diagram showing the configuration of the microscope control device 20 of the first embodiment. Regarding the microscope device 10, a block diagram of a part of the configuration controlled by each part of the microscope control device 20 is shown.

The microscope control device 20 includes a CPU (Central Processing Unit) 21, a primary storage unit 24, and the like.
It is composed of a computer provided with a secondary storage unit 25, an external I / F (Interface) 27, and the like. The CPU 21 includes a control unit 22 and a processing unit 23, and controls the entire microscope observation system 1. The primary storage unit 24 is a volatile memory used as a work area or the like when executing various programs. An example of the primary storage unit 24 is a RAM (Random Access Memory). The secondary storage unit 25 is a non-volatile memory in which various programs, various parameters, and the like are stored in advance, and one embodiment of the photographing control program 26 of the present invention is installed. When the photographing control program 26 is executed by the CPU 21, the control unit 22 and the processing unit 23 function. Further, the secondary storage unit 25 stores shape information 29, which will be described later. Examples of the secondary storage unit 25 include EEPROM (Electrically Erasable Programmable Read-Only Memory), flash memory, and the like. The external I / F 27 controls the transmission and reception of various information between the microscope device 10 and the microscope control device 20. The CPU 21, the primary storage unit 24, and the secondary storage unit 25 are connected to the bus line 28. The external I / F 27 is also connected to the bus line 28.

The shooting control program 26 is recorded and distributed on a recording medium such as a DVD (Digital Versatile Disc) and a CD-ROM (Compact Disc Read Only Memory), and is installed in a computer from the recording medium. Alternatively, the shooting control program 26 is stored in the storage device or network storage of the server computer connected to the network in a state of being accessible from the outside, and is downloaded to the computer in response to a request from the outside, and then installed. It may be done.

The shape information 29 is shape information of the bottom surface, that is, the installation surface of the culture container 50S, which is predetermined by the user. The shape information of the bottom surface of the culture vessel 50S is measured in advance using, for example, a laser displacement meter. FIG. 7 is a diagram for explaining the shape information of the bottom surface of the culture container 50S. As shown in FIG. 7, the shape information of the present embodiment is information obtained by measuring the bottom surface 50a of the culture vessel 50S in the XY directions with a spatial resolution of 10 μm × 10 μm. The spatial resolution of the shape information is not limited to this. Further, the method for measuring the shape information of the bottom surface 50a of the culture vessel 50S is not limited to the measurement by the laser displacement meter, and if the method can measure in the order of 10 μm, other methods such as the confocal method and the spectral interference method can be used. It may be measured.

Further, the shape information of the bottom surface 50a of the culture container 50S may be measured by the detection unit 18 provided in the microscope device 10 by installing the culture container 50S predetermined by the user on the stage 51. , The table in which the identification information of the culture container 50S and the shape information measured in advance are associated with each other may be stored in the secondary storage unit 25. Then, the user sets and inputs the identification information of the culture container 50S predetermined by the user using the input device 40, and reads out the shape information of the culture container 50S having the identification information from the secondary storage unit 25. May be good. Further, the identification information of the culture vessel 50S is not set and input by the user, but a barcode or QR (Quick Response) code (registered trademark) or the like is given to the culture vessel 50S, and the barcode or QR code (registration) is given. Identification information may be obtained by reading the trademark). The identification information of the culture container 50S may be, for example, the model number of the manufacturer or the serial number. The table may not necessarily be stored in the secondary storage unit 25, and the CPU 21 may derive the shape information measured in advance from the identification information of the culture container 50S.

Further, although the case where the general-purpose computer functions as the microscope control device 20 has been described above, it may be carried out by a dedicated computer. The dedicated computer may be firmware that executes a program recorded in the non-volatile memory such as a built-in ROM (Read Only Memory) or a flash memory. Further, a dedicated circuit such as an ASIC (Application Specific Integrated Circuit) or an FPGA (field programmable gate arrays) that permanently stores a program for executing at least a part of the functions of the microscope control device 20. May be provided. Alternatively, the program instructions stored in the dedicated circuit may be combined with the program instructions executed by the general-purpose CPU programmed to use the program of the dedicated circuit. As described above, program instructions may be executed in any combination of computer hardware configurations.

The control unit 22 controls the imaging optical system drive unit 15 based on the position information of the bottom surface of the culture vessel 50 in the Z direction detected by the detection unit 18 as described above. Then, the objective lens 14b of the imaging optical system 14 moves in the optical axis direction by driving the imaging optical system driving unit 15, and autofocus control is performed. Further, the control unit 22 drives and controls the horizontal drive unit 17, thereby moving the stage 51 in the X direction and the Y direction. The horizontal drive unit 17 is composed of an actuator having a piezoelectric element or the like.

In the present embodiment, the stage 51 is moved in the X and Y directions under the control of the control unit 22, the imaging optical system 14 is scanned two-dimensionally in the culture vessel 50, and each observation by the imaging optical system 14 is performed. An image of the phase difference of the position is taken. That is, phase difference images for each of a plurality of imaging regions (fields of view) divided in one well are captured.

The control unit 22 also functions as a display control unit that displays a single composite retardation image generated by combining the phase difference images of each observation position taken by the microscope device 10 on the display device 30. ..

Here, in the culture container 50 used for microscopic observation, the surface treatment of the inner surface of the culture container 50, the material of the container, and the like may differ depending on the type of the culture container 50, for example, the difference in the manufacturer. If the surface treatment and the material of the container are different, the culture state of the observation target housed in the culture container 50 and the shape of the meniscus formed on the surface of the liquid will be different, and the optical conditions and the like will be photographed. Conditions may change. Further, in general, the culture vessel 50 is often a disposable type, and the manufacturing accuracy is not very good. The deflection (unevenness) formed on the bottom surface 50a of the culture container 50 also differs depending on the type of the culture container 50, such as a difference in the manufacturer, and the range of manufacturing error may also differ.

On the other hand, since the bottom surface 50a of the culture container 50 has a deflection, the imaging optical system drive unit 15 moves the objective lens 14b in the optical axis direction for each observation position based on the shape information of the bottom surface 50a of the culture container 50. Therefore, it is necessary to perform autofocus control to adjust the focus position. However, the deflection formed on the bottom surface 50a of the culture vessel 50 differs depending on the type of the culture vessel 50, for example, the manufacturer differs. Therefore, when the imaging conditions of the microscope device 10 are set in the culture container 50S of the type to be installed in the predetermined microscope device 10, that is, the culture container 50S intended by the user, the culture container 50S other than the culture container 50S intended by the user is set. When the culture vessel 50 of the above is installed in the microscope device 10, the set imaging conditions may not be suitable for the culture vessel 50 installed in the microscope device 10.

For example, when the deflection of the bottom surface 50a of the culture container 50, that is, the height difference of the bottom surface 50a of the culture container 50 is larger than the movable range in which the piezoelectric element 15A moves the objective lens 14b in the Z direction, the piezoelectric element 15A is used. When the focus control is performed, the movable range may be exceeded, so that the focal position may not be aligned and the captured image captured by the imaging unit 16 may become a blurred image. When the photographed image becomes a blurred image, it is necessary to change the culture container 50 to the culture container 50S intended by the user and start over from the observation target, that is, the culture of cells. The height difference of the bottom surface 50a of the culture container 50S intended by the user does not exceed the movable range when the focus is controlled by the piezoelectric element 15A. That is, when the height difference of the bottom surface 50a of the culture container 50S does not exceed the movable range, the actuator is previously operated so that the movement of the objective lens 14b in the Z direction does not deviate from the driveable range of the piezoelectric element 15A. By moving the piezoelectric element 15A in the Z direction by the 15B, the position of the driveable range of the piezoelectric element 15A is adjusted.

When the shape information of the bottom surface 50a of the culture container 50 in which the observation target is housed is different from the shape information of the bottom surface of the culture container 50S, the control unit 22 of the present embodiment determines the culture container 50S in advance. The imaging condition is changed from the imaging condition based on the shape information of the bottom surface of the culture vessel 50 to the imaging condition based on the shape information of the bottom surface 50a of the culture container 50 containing the observation target, and the imaging unit 16 is made to image.

The control unit 22 as an example of the present embodiment causes the detection unit 18 to perform a pre-measurement for measuring the shape of the bottom surface 50a of the culture container 50 containing the observation target before the main imaging by the imaging unit 16. As a result, the height of the bottom surface 50a of the culture vessel 50 is acquired as the shape information of the bottom surface 50a of the culture vessel 50 in which the observation target is housed. The pre-measurement by the detection unit 18 is as described above.

Further, the control unit 22 acquires the height difference of the bottom surface 50a of the culture container 50 from the acquired height value of the bottom surface 50a of the culture container 50, and the height difference is such that the piezoelectric element 15A makes the objective lens 14b in the optical axis direction. When the size of the movable range is larger than the size of the movable range, the control unit 22 drives the actuator 15B according to the height of the bottom surface 50a of the culture container 50 to move the piezoelectric element 15A in the Z direction. The position of the piezoelectric element 15A in the driveable range in the Z direction is changed, and the imaging unit 16 is made to perform the main shooting. Specifically, the actuator 15B is driven when the focus position of the objective lens 14b based on the height of the bottom surface 50a of the culture vessel 50 is out of the movable range of the piezoelectric element 15A. As a result, focus control can be automatically performed according to the shape of the height of the bottom surface 50a of the culture vessel 50, so that the time and effort to change the culture vessel 50 to a predetermined culture vessel 50S, that is, the culture vessel 50S intended by the user, or again. The time required to reculture the cells can be reduced, and the deterioration of the image quality of the captured image due to the mistake of the container can be suppressed.

Next, returning to FIG. 5, the processing unit 23 performs various processing such as gamma correction, luminance / color difference conversion, and compression processing on the image signal acquired by the imaging unit 16. Further, the processing unit 23 outputs the image signal obtained by performing various processing to the control unit 22 for each frame at a specific frame rate. Further, the processing unit 23 generates one composite retardation image by combining the retardation images of each observation position R taken by the microscope device 10.

Further, the input device 40 and the display device 30 are connected to the microscope control device 20 by a bus line 28.

The display device 30 displays a composite phase difference image generated by the control unit 22 as described above, and includes, for example, a liquid crystal display or the like. Further, the display device 30 may be configured by a touch panel and may also be used as the input device 40.

The input device 40 includes a mouse, a keyboard, and the like, and accepts various setting inputs by the user. The input device 40 of the present embodiment receives setting inputs such as an instruction to change the magnification of the retardation lens 14a and an instruction to change the moving speed of the stage. In addition, it accepts a setting input of identification information of the culture container 50S predetermined by the user.

Next, the processing performed by the microscope observation system 1 of the present embodiment will be described. FIG. 8 is a flowchart of processing performed in the microscope observation system 1 of the present embodiment.

First, as shown in FIG. 8, the control unit 22 irradiates the detection unit 18 with light on the bottom surface 50a of the culture container 50 in which the observation target S is housed (step ST1), and the detection unit 18 of the culture container 50. The reflected light reflected on the bottom surface 50a is detected (step ST2). Next, the control unit 22 acquires the height of the bottom surface 50a of the culture container 50 based on the reflected light detected by the detection unit 18 (step ST3).

Next, the height acquired by the control unit 22 is different from the height of the culture container 50S stored as the shape information 29 in the secondary storage unit 25, that is, the height of the bottom surface of the predetermined culture container 50S. When the determination is made (step ST4; YES), the control unit 22 causes the CPU 21 to change the shooting conditions (step ST5).

Here, FIG. 9 shows a flowchart of the imaging condition changing process performed in the microscope observation system 1 of the present embodiment.

As shown in FIG. 9, the control unit 22 first drives the CPU 21 to acquire the height difference of the bottom surface 50a from the height of the bottom surface 50a of the culture vessel 50 acquired in the process of step ST3 of FIG. 8 (step). ST11).

Next, the control unit 22 acquires the size of the movable range of the piezoelectric element 15A stored in the secondary storage unit 25 (step ST12). When the control unit 22 determines that the height difference is larger than the size of the movable range (step ST13; YES), the control unit 22 sets the height of the bottom surface 50a of the culture vessel 50 with respect to the actuator 15B. The position of the movable range of the piezoelectric element 15A is changed accordingly (step ST14). Specifically, when the focus position of the objective lens 14b based on the height of the bottom surface 50a of the culture vessel 50 is out of the movable range of the piezoelectric element 15A, the objective lens 14b is moved by driving the actuator 15B. The shooting conditions are changed by changing the position of the piezoelectric element 15A in the movable range so that the control unit 22 can move to the focus position.

Next, returning to FIG. 8, the CPU 21 shifts the processing to step ST6, and the control unit 22 causes the imaging unit 16 to perform the main shooting using the changed shooting conditions (step ST6).

On the other hand, when it is determined in step ST4 that the height acquired by the control unit 22 is not different from the height of the bottom surface of the predetermined culture vessel 50S (step ST4; NO), the CPU 21 processes the process to step ST6. After the transition, the control unit 22 causes the imaging unit 16 to perform the main shooting using the preset shooting conditions (step ST6).

As described above, the image is taken by the microscope observation system 1. The captured phase difference images of the observation positions R of the observation target S are combined by the processing unit 23 to generate one composite retardation image, and the generated composite retardation image is displayed by the control unit 22 by the display device 30. Is displayed in.

According to the microscope observation system 1 of the above embodiment, the control unit 22 has different shape information of the bottom surface 50a of the culture container 50 in which the observation target S is housed from the shape information of the bottom surface 50a of the culture container 50 defined in advance. In this case, the imaging condition is changed from the predetermined imaging condition based on the shape information of the bottom surface 50a of the culture vessel 50 to the imaging condition based on the shape information of the bottom surface 50a of the culture vessel 50 containing the observation target S. The imaging unit 16 can perform imaging under imaging conditions suitable for the shape of the bottom surface 50a of the culture vessel 50 in which the observation target S is housed, and the image quality of the captured image due to an error in the culture vessel 50 can be obtained. The decrease can be suppressed.

Next, the microscope observation system 1-2 using the second embodiment of the imaging control device of the present invention will be described. The microscope observation system 1-2 of the present embodiment differs only from the configuration of the microscope observation system 1 of the first embodiment described shown in FIGS. 1 to 5 and the configuration corresponding to the measurement unit of the present invention. Therefore, only the measuring unit will be described below, and the description of other configurations will be omitted.

In the above embodiment, the detection unit 18 is an example of the measurement unit of the present invention that performs pre-measurement, whereas in the microscope observation system 1-2 of the present embodiment, the measurement unit of the present invention that performs pre-measurement is As an example, it has an imaging unit 16. The measuring unit of the present embodiment performs pre-measurement in which the observation target S housed in the culture container 50 is pre-photographed in the imaging unit 16 before the main imaging by the imaging unit 16.

The control unit 22 acquires a photographed image by causing the imaging unit 16 to perform pre-measurement, and based on the acquired photographed image, serves as shape information of the bottom surface 50a of the culture container 50 as the curvature of the bottom surface 50a of the culture container 50. To get. Specifically, the pixel value of the acquired captured image is acquired, and the curvature is calculated based on the acquired pixel value.

Specifically, when using a well plate having 96 wells in which cells are cultured as the culture vessel 50, the value of the position of the default focus in the Z direction, for example, the user manually observes in advance. With the combined value of the position in the Z direction as 0, prescan is performed at intervals of 10 μm in the range of −150 μm to +150 μm in the Z direction, and the measurement data of a total of 31 prescans is acquired. For the measurement data for 31 measurements, in order to increase the processing speed, only 48 fields of view, which are odd rows of the well plate, were photographed in each measurement, and the contrast in the image of each field of view acquired by photographing. Calculate the average value of each. In each of the 48 fields of view, one well is imaged. Then, in each of the 48 visual fields, the value of the position in the Z direction where the average value of the contrast is the largest is obtained, and the coordinate position in the XY directions of the 48 visual fields, that is, the measurement position and the above Z in this measurement position. Obtain the curvature from the value of the position in the direction.

Next, the processing performed by the microscope observation system 1-2 of the present embodiment will be described. FIG. 10 is a flowchart of processing performed in the microscope observation system 1-2 of the present embodiment.

First, as shown in FIG. 10, the control unit 22 causes the imaging unit 16 to image the observation target S housed in the culture container 50 (step ST21), and acquires a photographed image (step ST22). Next, the control unit 22 acquires the curvature of the bottom surface 50a of the culture vessel 50 based on the acquired captured image (step ST33).

Next, the curvature acquired by the control unit 22 is different from the curvature of the bottom surface of the culture container 50S stored as the shape information 29 in the secondary storage unit 25, that is, the curvature of the bottom surface of the culture container 50S determined in advance. When the determination is made (step ST24; YES), the control unit 22 causes the CPU 21 to change the shooting conditions (step ST25).

Here, FIG. 11 shows a flowchart of the imaging condition changing process performed in the microscope observation system 1-2 of the present embodiment.

First, as shown in FIG. 11, the control unit 22 irradiates the detection unit 18 with light on the bottom surface 50a of the culture container 50 in which the observation target S is housed (step ST31), and the detection unit 18 of the culture container 50. The reflected light reflected on the bottom surface 50a is detected (step ST32). Next, the control unit 22 acquires the height of the bottom surface 50a of the culture container 50 based on the reflected light detected by the detection unit 18 (step ST33).

Next, the control unit 22 drives the CPU 21 to acquire the height difference of the bottom surface 50a from the height of the bottom surface 50a of the culture vessel 50 acquired in the process of step ST33 of FIG. 11 (step ST34).

Next, the control unit 22 acquires the size of the movable range of the piezoelectric element 15A stored in the secondary storage unit 25 (step ST35). When the control unit 22 determines that the height difference is larger than the size of the movable range (step ST36; YES), the control unit 22 sets the height of the bottom surface 50a of the culture vessel 50 with respect to the actuator 15B. The position of the movable range of the piezoelectric element 15A is changed accordingly (step ST37). Specifically, when the focus position of the objective lens 14b based on the height of the bottom surface 50a of the culture vessel 50 is out of the movable range of the piezoelectric element 15A, the objective lens 14b is moved by driving the actuator 15B. The shooting conditions are changed by changing the position of the piezoelectric element 15A in the movable range so that the control unit 22 can move to the focus position.

Next, returning to FIG. 10, the CPU 21 shifts the processing to step ST26, and the control unit 22 causes the imaging unit 16 to perform the main shooting using the changed shooting conditions (step ST26).

On the other hand, when it is determined that the curvature acquired by the control unit 22 in step ST24 is not different from the curvature of the bottom surface of the predetermined culture vessel 50S (step ST24; NO), the CPU 21 shifts the process to step ST26. Then, the control unit 22 causes the imaging unit 16 to perform the main shooting using the preset shooting conditions (step ST26).

As described above, imaging is performed by the microscope observation system 1-2. The captured phase difference images of the observation positions R of the observation target S are combined by the processing unit 23 to generate one composite retardation image, and the generated composite retardation image is displayed by the control unit 22 by the display device 30. Is displayed in.

According to the microscope observation system 1-2 of the above embodiment, the control unit 22 determines that the shape information of the bottom surface 50a of the culture container 50 in which the observation target S is housed is the shape information of the bottom surface 50a of the culture container 50 that is predetermined. If the image is different from the above, the imaging condition is changed from the predetermined imaging condition based on the shape information of the bottom surface 50a of the culture vessel 50 to the imaging condition based on the shape information of the bottom surface 50a of the culture vessel 50 containing the observation target S. Since the imaging unit 16 is allowed to take an image, the imaging unit 16 can take an image under imaging conditions suitable for the shape of the bottom surface 50a of the culture container 50 in which the observation target S is housed, and the photographed image due to an error in the culture container 50 can be photographed. It is possible to suppress deterioration of image quality.

Next, the microscope observation system 1-3 using the third embodiment of the imaging control device of the present invention will be described. The microscope observation system 1-3 of the present embodiment includes the notification unit of the present invention in the configuration of the microscope observation system 1 of the first embodiment described as shown in FIGS. 1 to 5. Therefore, only the notification unit will be described below, and the description of other configurations will be omitted.

The notification unit of the present invention receives a command from the control unit 22 when the shape information of the bottom surface 50a of the culture container 50 containing the observation target S is different from the shape information of the bottom surface 50a of the culture container 50 defined in advance. Notify that they are different. In the microscope observation system 1-3 of the present embodiment, the notification unit of the present invention is configured by the display device 30 as an example. The display device 30 as a notification unit is composed of a display, and displays, for example, "the culture container is different" on the screen by a command from the control unit 22.

In the display device 30 of the above embodiment, the control unit 22 warns the user that the culture containers are different by visually displaying a message or the like indicating that the culture containers are different on the display. Although the case has been illustrated, the technique of the present invention is not limited thereto. For example, it may be an audible display in which audio is output by an audio reproduction device, or a permanent visible display in which audio is recorded on a recording medium such as paper using a printer. Further, it is a display by a combination of at least two or more of a visible display by a display, an audible display by outputting sound by an audio reproduction device, and a permanent visible display recorded on a recording medium such as paper by using a printer. You may. In addition, it may be notified that the culture vessels are different by means of communication such as e-mail or telephone, or it may be notified that the culture vessels are different by turning on or blinking the indicator lamp. At least two or more of the above notification methods may be combined to notify that the culture vessels are different.

Next, the processing performed by the microscope observation system 1-3 of the present embodiment will be described. FIG. 12 is a flowchart of processing performed in the microscope observation system 1-3 of the present embodiment. The processes of steps ST41 to ST44 performed in the microscope observation system 1-3 of the present embodiment are the processes performed in the microscope observation system 1 of the first embodiment in steps ST1 to ST4 of the flowchart shown in FIG. Since it is the same as the processing, the description here is omitted, and only the different parts will be described.

As shown in FIG. 12, the height acquired by the control unit 22 is the height of the culture container 50S stored as shape information 29 in the secondary storage unit 25, that is, the height of the bottom surface of the culture container 50S determined in advance. When it is determined that they are different (step ST44; YES), the control unit 22 notifies (displays) that they are different (step ST45) to the display device 30 as described above, and a series of series. The process ends.

According to the microscopic observation system 1-3 of the above embodiment, the control unit 22 determines that the shape information of the bottom surface 50a of the culture container 50 in which the observation target S is housed is the shape information of the bottom surface 50a of the culture container 50 that is predetermined. When the difference is different from the above, the display device 30 is displayed to indicate that the difference is obtained, so that the culture container 50 containing the observation target S to be photographed is not the user's desired, that is, the predetermined culture container 50S. Since the user can know, measures are taken such as replacing the imaging target with an observation target housed in the predetermined culture container 50S, or re-culturing the observation target in the predetermined culture container 50S. be able to. Therefore, since it is possible to prevent the control unit 22 from causing the image pickup unit 16 to take a photographed image having a deteriorated image quality, it is possible to suppress the deterioration of the image quality of the photographed image due to an error in the culture container 50.

In the microscope observation system 1-3 of the above embodiment, the imaging optical system drive unit 15 includes the piezoelectric element 15A and the actuator 15B, but the present invention is not limited to this, and only the piezoelectric element 15A is provided. It may be provided with.

Next, the microscope observation system 1-4 using the fourth embodiment of the imaging control device of the present invention will be described. The microscope observation system 1-4 of the present embodiment includes the notification unit of the present invention in the configuration of the microscope observation system 1 of the first embodiment described as shown in FIGS. 1 to 5. Since the same notification unit as that provided in the microscope observation system 1-3 of the third embodiment can be used as the notification unit, the description thereof is omitted here.

Next, the processing performed by the microscope observation system 1-4 of the present embodiment will be described. FIG. 13 is a flowchart of processing performed in the microscope observation system 1-4 of the present embodiment. The processing of steps ST51 to ST54 performed in the microscope observation system 1-4 of the present embodiment is a step from step ST21 of the flowchart shown in FIG. 10 of the processing performed in the microscope observation system 1-2 of the second embodiment. Since it is the same as the processing of ST24, the description here is omitted, and only the different parts will be described.

As shown in FIG. 13, the curvature acquired by the control unit 22 is different from the curvature of the culture container 50S stored as the shape information 29 in the secondary storage unit 25, that is, the curvature of the bottom surface of the culture container 50S determined in advance. When it is determined that the condition is present (step ST54; YES), the control unit 22 notifies (displays) that the display device 30 is different (step ST55), and the series of processes is completed.

According to the microscopic observation system 1-4 of the above embodiment, the control unit 22 determines that the shape information of the bottom surface 50a of the culture container 50 in which the observation target S is housed is the shape information of the bottom surface 50a of the culture container 50 that is predetermined. When the difference is different from the above, the display device 30 is displayed to indicate that the difference is obtained, so that the culture container 50 containing the observation target S to be photographed is not the user's desired, that is, the predetermined culture container 50S. Since the user can know, measures are taken such as replacing the imaging target with an observation target housed in the predetermined culture container 50S, or re-culturing the observation target in the predetermined culture container 50S. be able to. Therefore, since it is possible to prevent the control unit 22 from causing the image pickup unit 16 to take a photographed image having a deteriorated image quality, it is possible to suppress the deterioration of the image quality of the photographed image due to an error in the culture container 50.

In the microscope observation system 1-4 of the above embodiment, the imaging optical system drive unit 15 includes the piezoelectric element 15A and the actuator 15B, but the present invention is not limited to this, and only the piezoelectric element 15A is provided. It may be provided with.

Next, the microscope observation system 1-5 using the fifth embodiment of the imaging control device of the present invention will be described. As the microscope observation system 1-5 of the present embodiment, the same configuration as that of the microscope observation system 1 of the first embodiment described with reference to FIGS. 1 to 5 can be used. Omit.

In the microscope observation system 1-5 of the present embodiment, the identification information of the culture container 50S predetermined by the user is stored as the shape information 29 in the secondary storage unit 25. Further, the culture container 50 in which the observation target S is housed is given a barcode or QR code (registered trademark) associated with the identification information of the culture container 50 in advance, and the barcode or QR code (registered trademark) is assigned. ) Is read using the input device 40 to acquire the identification information. The identification information of the culture container 50 may be, for example, the model number of the manufacturer or the serial number.

Next, the processing performed by the microscope observation system 1-5 of the present embodiment will be described. FIG. 14 is a flowchart of processing performed in the microscope observation system 1-5 of the present embodiment.

As shown in FIG. 5, first, the control unit 22 receives the identification information of the culture container 50 containing the observation target S input by the user using the input device 40 (step S61), and the observation target S is housed. The identification information of the culture vessel 50 is acquired (step ST62). Next, the control unit 22 determines that the acquired identification information is different from the identification information of the culture container 50S stored as the shape information 29 in the secondary storage unit 25, that is, the identification information of the culture container 50S predetermined. If this is the case (step ST63; YES), the control unit 22 causes the CPU 21 to change the shooting conditions (step ST64). Since the process of changing the imaging conditions is the same as the process of changing the imaging conditions of FIG. 11 performed in the microscope observation system 1-2 of the second embodiment described above, the description thereof is omitted here.

Next, the CPU 21 shifts the processing to step ST65, and the control unit 22 causes the imaging unit 16 to perform the main shooting using the changed shooting conditions (step ST65).

On the other hand, when it is determined in step ST63 that the identification information acquired by the control unit 22 is not different from the identification information of the culture container 50S determined in advance (step ST63; NO), the CPU 21 shifts the process to step ST65. Then, the control unit 22 causes the imaging unit 16 to perform the main shooting using the preset shooting conditions (step ST65).

As described above, imaging is performed by the microscope observation system 1-5. The captured phase difference images of the observation positions R of the observation target S are combined by the processing unit 23 to generate one composite retardation image, and the generated composite retardation image is displayed by the control unit 22 by the display device 30. Is displayed in.

According to the microscope observation system 1-5 of the above embodiment, the control unit 22 determines that the shape information of the bottom surface 50a of the culture container 50 in which the observation target S is housed is the shape information of the bottom surface 50a of the culture container 50 that is predetermined. If the image is different from the above, the imaging condition is changed from the predetermined imaging condition based on the shape information of the bottom surface 50a of the culture vessel 50 to the imaging condition based on the shape information of the bottom surface 50a of the culture vessel 50 containing the observation target S. Since the imaging unit 16 is allowed to take an image, the imaging unit 16 can take an image under imaging conditions suitable for the shape of the bottom surface 50a of the culture container 50 in which the observation target S is housed, and the photographed image due to an error in the culture container 50 can be photographed. It is possible to suppress deterioration of image quality.

Next, the microscope observation system 1-6 using the sixth embodiment of the imaging control device of the present invention will be described. The microscope observation system 1-6 of the present embodiment includes the notification unit of the present invention in the configuration of the microscope observation system 1 of the first embodiment described as shown in FIGS. 1 to 5. Since the same notification unit as that provided in the microscope observation system 1-3 of the third embodiment can be used as the notification unit, the description thereof is omitted here.

Next, the processing performed by the microscope observation system 1-6 of the present embodiment will be described. FIG. 15 is a flowchart of processing performed in the microscope observation system 1-6 of the present embodiment. The processing of steps ST71 to ST73 performed in the microscope observation system 1-6 of the present embodiment is a step from step ST61 of the flowchart shown in FIG. 14 of the processing performed in the microscope observation system 1-5 of the fifth embodiment. Since it is the same as the processing of ST63, the description here is omitted, and only the different parts will be described.

As shown in FIG. 15, the identification information acquired by the control unit 22 is different from the identification information of the culture container 50S stored as the shape information 29 in the secondary storage unit 25, that is, the predetermined identification information of the culture container 50S. When it is determined that the case is (step ST73; YES), the control unit 22 notifies (displays) that the display device 30 is different (step ST74), and the series of processes is completed.

According to the microscope observation system 1-6 of the above-described embodiment, the control unit 22 determines that the shape information of the bottom surface 50a of the culture container 50 in which the observation target S is housed is the shape information of the bottom surface 50a of the culture container 50. When the difference is different from the above, the display device 30 is displayed to indicate that the difference is obtained, so that the culture container 50 containing the observation target S to be photographed is not the user's desired, that is, the predetermined culture container 50S. Since the user can know, measures are taken such as replacing the imaging target with an observation target housed in the predetermined culture container 50S, or re-culturing the observation target in the predetermined culture container 50S. be able to. Therefore, since it is possible to prevent the control unit 22 from causing the image pickup unit 16 to take a photographed image having a deteriorated image quality, it is possible to suppress the deterioration of the image quality of the photographed image due to an error in the culture container 50.

In the microscope observation system 1-6 of the above embodiment, the imaging optical system drive unit 15 includes the piezoelectric element 15A and the actuator 15B, but the present invention is not limited to this, and only the piezoelectric element 15A is provided. It may be provided with.

Next, the microscope observation system 1-7 using the seventh embodiment of the imaging control device of the present invention will be described. FIG. 16 shows a block diagram showing the configuration of the microscope observation system 1-7 of the present embodiment. As shown in FIG. 16, the microscope observation system 1-7 of the present embodiment includes a vertical drive unit 19 in the configuration of the microscope observation system 1 of the first embodiment described and described in FIG. .. Further, in the present embodiment, the imaging optical system drive unit 15 does not have to include the actuator 15B.

The vertical drive unit 19 is composed of an actuator having a pulse motor or the like. The vertical drive unit 19 is driven and controlled by the control unit 22 to move the stage 51 in the Z direction, that is, in the optical axis direction. The vertical drive unit 19 is an example of the optical axis drive unit of the present invention.

In the microscope observation systems 1 to 1-6 of the first to sixth embodiments described above, the control unit is used to move the culture vessel 50 containing the observation target S relative to the imaging optical system 14. The 22 drives the actuator 15B to move the objective lens 14b, that is, the imaging optical system 14 in the Z direction. On the other hand, in the microscope observation system 1-7 of the present embodiment, the control unit 22 moves in the vertical direction in order to move the culture container 50 containing the observation target S relative to the imaging optical system 14. The stage 51 is moved in the Z direction by driving the drive unit 19.

In the configuration of the microscope observation system 1-7 of the present embodiment, the imaging optical system drive unit 15 may include an actuator 15B. In this case, the control unit 22 drives at least one of the actuator 15B and the vertical drive unit 19 in order to move the culture container 50 containing the observation target S relative to the imaging optical system 14. As a result, the stage 51 is moved in the Z direction.

Although the above embodiment applies the present invention to a phase-contrast microscope, the present invention can be applied not only to a phase-contrast microscope but also to other microscopes such as a differential interference microscope and a bright-field microscope. ..

Further, in each of the above embodiments, the case where the photographing control program 26 is read from the secondary storage unit 25 is illustrated, but it is not always necessary to store the imaging control program 26 in the secondary storage unit 25 from the beginning. For example, as shown in FIG. 17, SSD (Solid State Drive), USB (Universal Serial Bus) memory, or DVD-ROM (Digital).
The photographing control program 26 may be first stored in an arbitrary portable storage medium 250 such as versail disc-Read Only Memory). In this case, the imaging control program 26 of the storage medium 250 is installed in the microscope observation system 1, and the installed imaging control program 26 is executed by the CPU 21.

Further, the imaging control program 26 is stored in a storage unit of another computer or server device connected to the microscope apparatus 10 via a communication network (not shown), and the imaging control program 26 responds to the request of the microscope apparatus 10. It may be downloaded accordingly. In this case, the downloaded shooting control program 26 is executed by the CPU 21.

Further, the photographing control process described in each of the above embodiments is merely an example. Therefore, it goes without saying that unnecessary steps may be deleted, new steps may be added, or the processing order may be changed within a range that does not deviate from the purpose.

Further, in each of the above embodiments, the case where the shooting control process is realized by the software configuration using the computer is illustrated, but the technique of the present disclosure is not limited to this. For example, instead of software configuration using a computer, FPGA (Field-Programmable Gate Array) or ASIC (Application)
The shooting control process may be executed only by the hardware configuration such as (Special Integrated Circuit). The shooting control process may be executed by a configuration in which a software configuration and a hardware configuration are combined.

All documents, patent applications and technical standards described herein are described herein to the same extent as if the individual documents, patent applications and technical standards were specifically and individually stated to be incorporated by reference. Incorporated by reference in the document.

Hereinafter, the action and effect of this embodiment will be described.

When the shape information of the bottom surface of the container in which the observation target is housed is different from the shape information of the bottom surface of the predetermined container, the notification unit is notified that the information is different, or the shape information of the bottom surface of the predetermined container is different. Since the imaging conditions are changed from the imaging conditions based on the shape information to the imaging conditions based on the shape information of the bottom surface of the container containing the observation target, the imaging unit is made to photograph, so that the deterioration of the image quality of the captured image due to the mistake of the container is suppressed. it can.

1 Microscope observation system 10 Microscope device 11 White light source 12 Condenser lens 13 Slit plate 14 Imaging optical system 14a Phase difference lens 14b Objective lens 14c Phase plate 14d Imaging lens 15 Imaging optical system drive unit 16 Imaging unit 17 Horizontal drive unit 18 Detection unit 19 Vertical drive unit 20 Microscope control device 21 CPU
22 Control unit 23 Processing unit 24 Primary storage unit 25 Secondary storage unit 26 Imaging control program 27 External I / F
28 Bus line 29 Shape information 30 Display device 40 Input device 50 Culture container 50S Predetermined culture container 50a Bottom surface 50b Bottom surface 51 Stage 51a Opening L Illumination light C Culture solution S Observation target

Claims (10)

When the shape information of the bottom surface of the container in which the observation target is housed is different from the shape information of the bottom surface of the predetermined container, the notification unit is notified that the information is different, or the shape information of the bottom surface of the predetermined container is different. An imaging control device including a control unit that changes the imaging conditions based on the shape information to the imaging conditions based on the shape information of the bottom surface of the container containing the observation target and causes the imaging unit to take an image. The control unit causes the measuring unit to perform pre-measurement for measuring the shape of the bottom surface of the container in which the observation target is housed before the main shooting by the imaging unit, so that the observation target is housed in the container. The imaging control device according to claim 1, wherein the shape information of the bottom surface is acquired. The control unit irradiates the measurement unit with light on the bottom surface of the container in which the observation target is housed, and acquires the height of the bottom surface of the container as the shape information based on the reflected light reflected by the bottom surface. 2. The imaging control device according to claim 2. The measuring unit has the imaging unit.
The imaging control device according to claim 2, wherein the control unit acquires the curvature of the bottom surface of the container as the shape information based on the captured image acquired by imaging the observation target housed in the container with the imaging unit. .. The imaging control device according to claim 3, wherein the measuring unit is a laser displacement sensor. An optical axis direction driving unit that moves the container containing the observation object relative to the optical axis direction of the imaging optical system with respect to the imaging optical system that forms an image of the observation target in the container. When the height difference of the bottom surface of the container in which the observation target is housed is larger than the size of the movable range in which the imaging optical system or the container is relatively moved in the optical axis direction, the control unit is the container. The imaging control device according to any one of claims 1 to 5, wherein the position of the range is changed with respect to the optical axis direction driving unit according to the height of the bottom surface, and the imaging unit is made to image. A shape information storage unit for storing the shape information of the container is provided.
The imaging control device according to claim 1, wherein the shape information storage unit stores a table in which the identification information of the container in which the observation target is housed and the shape information of the bottom surface of the container are stored. The imaging control device according to any one of claims 1 to 7, wherein the container is a dish, a well plate, or a flask. It is a method of operating an imaging control device including a control unit.
When the shape information of the bottom surface of the container in which the observation target is housed is different from the shape information of the bottom surface of the container, the control unit notifies the notification unit that the shape information is different, or is predetermined. A method of operating an imaging control device in which an imaging unit is made to photograph by changing from imaging conditions based on the shape information of the bottom surface of the container to imaging conditions based on the shape information of the bottom surface of the container containing the observation target. Computer,
When the shape information of the bottom surface of the container in which the observation target is housed is different from the shape information of the bottom surface of the predetermined container, the notification unit is notified that the information is different, or the shape information of the bottom surface of the predetermined container is different. An imaging control program for changing the imaging conditions based on the shape information to the imaging conditions based on the shape information of the bottom surface of the container in which the observation target is housed so that the imaging unit functions as a control unit.