Microscope system, control device, and control method

Abstract

This system efficiently acquires images of specimens on multiple planes at different heights from the microscope stage. [Solution] A two-dimensional image sensor images the target specimen on the stage. The focusing device changes the distance between the objective lens and the stage. The control unit acquires specific parameters used for imaging the target specimen, selected from the parameters used for imaging each of several types of specimens according to the type of specimen. The parameters used for imaging each of several types of specimens include parameters used for imaging to acquire images of each of several types of specimens in each of several planes with different heights from the stage, at each of several positions in a plane parallel to the stage. The control unit controls the stage, the two-dimensional image sensor, and the focusing device based on the specific parameters to acquire images of the target specimen in each of several planes with different heights from the stage, at each of several positions in a plane parallel to the stage.

Description

Technical Field

[0001] The present invention relates to a microscope system, a control device for the microscope system, and a control method.

Background Art

[0002] In cytodiagnosis in pathological examinations using a microscope, a liquid-based cytology (LBC) specimen may be used. As an example, an LBC specimen is prepared by putting a specimen collected from a patient using a brush or the like into a vial together with a liquid and performing dispersion, cell collection, and cell transfer.

[0003] FIG. 1 shows an example of an LBC specimen. In the LBC specimen of FIG. 1, a plurality of cells 102 are overlapped and laminated on a slide glass 101. Therefore, the thickness of the LBC specimen becomes larger than the depth of field of the microscope, and it is difficult to image all cells with a single focal plane. Therefore, a method of generating a Z-stack image of the LBC specimen is used. By shifting the focal plane 103 little by little at a predetermined interval in the thickness direction of the LBC specimen and imaging, a Z-stack image can be generated.

[0004] Regarding Z-stack images, a system for generating and visualizing three-dimensional virtual slides is known (see, for example, Patent Document 1 and Patent Document 2). A scanning technique that achieves both high image quality and high throughput is also known (see, for example, Patent Document 3).

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Patent Document 2

Patent Document 3

Summary of the Invention

[0006] There are several methods for preparing LBC specimens. For example, comparing LBC specimens prepared using the existing methods M1 and M2, the shape of the cell application area on the slide glass is the same, but the area of ​​the application area for method M1 is larger than that for method M2. Also, the thickness of the LBC specimen prepared using method M2 is greater than that of the LBC specimen prepared using method M1. Thus, the application area and thickness of the LBC specimen can vary depending on the preparation method.

[0007] Therefore, in microscope systems that generate Z-stack images of LBC specimens prepared using multiple different methods, the parameters for generating the Z-stack image must be changed each time the LBC specimen being imaged is replaced, which increases the workload.

[0008] Furthermore, this problem arises not only when generating Z-stack images of LBC specimens prepared using multiple methods, but also when generating Z-stack images of various types of specimens.

[0009] In one aspect, the present invention aims to efficiently acquire images of a specimen in multiple planes at different heights from the microscope stage. [Means for solving the problem]

[0010] In one design, the microscope system includes an objective lens, a stage, a two-dimensional image sensor, a focusing mechanism, and a control unit. The two-dimensional image sensor images the target specimen on the stage. The focusing mechanism changes the distance between the objective lens and the stage.

[0011] The control unit acquires specific parameters used for imaging the target specimen, selected from among the parameters used for imaging each of multiple types of specimens, according to the type of specimen being imaged. The parameters used for imaging each of multiple types of specimens include parameters used for acquiring images of each of multiple types of specimens at multiple positions in a plane parallel to the stage, and at multiple planes with different heights from the stage.

[0012] The control unit controls the stage, the two-dimensional image sensor, and the focusing device based on specific parameters, thereby acquiring images of the target specimen at multiple positions in a plane parallel to the stage, and at multiple planes with different heights from the stage. [Effects of the Invention]

[0013] One aspect of this approach is that it allows for efficient acquisition of images of specimens in multiple planes at different heights from the microscope stage. [Brief explanation of the drawing]

[0014] [Figure 1] This is a diagram of an LBC specimen. [Figure 2] This is a diagram illustrating the configuration of a microscope system according to an embodiment. [Figure 3] This figure shows an LBC specimen on a glass slide with a label attached. [Figure 4] This is a diagram showing the focus point. [Figure 5] This is a diagram showing the plane of focus. [Figure 6] This is a diagram showing the configuration of a microscope device. [Figure 7] This is a diagram showing the specimen storage section. [Figure 8] This is a functional configuration diagram of the control device. [Figure 9] This is a flowchart of the first control process. [Figure 10] This is a diagram showing the parameter selection screen. [Figure 11]It is a flowchart of the second control process. [Figure 12] It is a flowchart of the third control process. [Figure 13] It is a flowchart of the fourth control process. [Figure 14] It is a flowchart of the fifth control process. [Figure 15] It is a flowchart of the correction process. [Figure 16] It is a hardware configuration diagram of the first information processing apparatus. [Figure 17] It is a hardware configuration diagram of the second information processing apparatus.

Embodiments of the Invention

[0015] Hereinafter, embodiments will be described in detail with reference to the drawings.

[0016] FIG. 2 shows a configuration example of the microscope system according to the embodiment. The microscope system of FIG. 2 includes a microscope device 201, a control device 202, and an image processing device 203, and generates a WSI (Whole Slide Imaging) image of a specimen. The microscope device 201, the control device 202, and the image processing device 203 are hardware.

[0017] The microscope device 201 communicates with the control device 202 and the image processing device 203 via a communication network 204. The communication network 204 is, for example, a LAN (Local Area Network) or a WAN (Wide Area Network).

[0018] The control device 202 selects a specific parameter from among the parameters used for imaging a plurality of types of specimens according to the type of the specimen to be imaged, and outputs the selected specific parameter to the microscope device 201.

[0019] Multiple types of specimens include, for example, multiple types of LBC specimens used in pathological examination and tissue specimens used in pathological examination. Multiple types of LBC specimens represent, for example, multiple preparation methods. Multiple preparation methods may be preparation method M1 and preparation method M2, or there may be three or more preparation methods including preparation method M1 and preparation method M2.

[0020] Tissue specimens are prepared by taking a portion of an organ or other tissue using a method called thin sectioning, and therefore have various planar shapes and are thin. For this reason, it is not necessary to generate a Z-stack image of a tissue specimen. A tissue specimen is an example of a given type of specimen.

[0021] The microscope device 201 scans the target specimen, which is wider than the actual field of view, to acquire multiple images of the target specimen and outputs them to the image processing device 203.

[0022] For example, if the specimen to be imaged is a tissue specimen, the microscope device 201 scans the entire area of ​​the specimen by repeatedly taking images while moving the imaging position in the X and Y directions relative to the specimen on the stage. The X and Y directions represent two mutually orthogonal directions in a plane parallel to the stage. The imaging position represents the position in the actual field of view indicated by the X and Y coordinates. In this case, the imaging position for each image is set so that the image acquired at that imaging position overlaps with a portion of the image acquired at an adjacent imaging position. The imaging positions are examples of positions in a plane parallel to the stage.

[0023] When the specimen to be imaged is a LBC specimen, the microscope device 201 not only scans the range of the specimen in the X and Y directions, but also moves the focal plane in the Z direction. For example, as shown in Figure 1, the microscope device 201 acquires images of the specimen in each of multiple planes parallel to the stage by slightly shifting the focal plane in the Z direction from the stage at each imaging position. Since the shape (planar shape, size, thickness, etc.) of LBC specimens prepared using the same preparation method is almost constant, the XYZ range required for image acquisition is constant for each preparation method.

[0024] The Z direction represents a direction perpendicular to the X and Y directions, and corresponds to the thickness direction of the LBC specimen.

[0025] When the specimen to be imaged is a tissue specimen, the image processing device 203 generates a 2D WSI image containing a single layer by stitching together multiple images in the X and Y directions output from the microscope device 201. The layer included in the 2D WSI image represents a single wide-field image generated by stitching together images acquired at multiple imaging positions along the focal plane. The focal plane represents a plane or curved surface that is in focus on numerous cells, etc., contained in the specimen to be imaged.

[0026] If the specimen to be imaged is an LBC specimen, the image processing device 203 generates a 3D WSI image containing multiple layers, in the same manner as in the case of a tissue specimen. The multiple layers included in the 3D WSI image include a wide-field image formed by stitching together images acquired at multiple imaging positions along the focal plane, and a predetermined number of wide-field images formed by stitching together images acquired at multiple imaging positions with the focus shifted above or below the focal plane.

[0027] Figure 3 shows an example of an LBC specimen on a glass slide with a label attached. Figures 3(a) and 3(b) are plan views of the upper surface of the glass slide 301.

[0028] Figure 3(a) shows an example of a glass slide 301 with a label 303 containing the string 304 attached. An LBC specimen 302 is coated onto the glass slide 301. The string 304 on the label 303 represents, for example, the name and preparation method of the LBC specimen 302. The string 304 is an example of a string indicating the type of specimen to be imaged.

[0029] Figure 3(b) shows an example of a glass slide 301 with a label 305 containing a two-dimensional code 306 attached. An LBC specimen 302 is coated onto the glass slide 301. The two-dimensional code 306 on the label 303 represents, for example, the preparation method of the LBC specimen 302 or the specimen ID. The specimen ID is the identification information of the LBC specimen 302. The two-dimensional code 306 is an example of a code that indicates the type or identification information of the specimen to be imaged.

[0030] The parameters used for imaging LBC specimen 302 include, for example, the imaging range of the specimen to be imaged, multiple focus points, Z step width, number of upper and lower layers of the focus plane.

[0031] The imaging range represents the coated area of ​​the LBC specimen 302 on the glass slide 301. If the LBC specimen 302 is prepared by preparation method M1 or preparation method M2, the shape of the coated area is circular. Therefore, the X and Y coordinates of the center position of the circle representing the coated area, and the size of that circle are set as the imaging range.

[0032] For example, the radius or diameter can be used as the size of the circle. The microscope device 201 acquires images of the LBC specimen 302 at each imaging position by scanning the imaging range in the X and Y directions. As an example, the size of the imaging range of an LBC specimen prepared by preparation method M1 is larger than the size of the imaging range of an LBC specimen prepared by preparation method M2.

[0033] The focus point represents a position within the imaging area that is used to generate the plane of focus.

[0034] Figure 4 shows an example of focus points. The symbol "+" within the imaging range 401 indicates the position of the focus point. In the example in Figure 4, 11 focus points are set. The position of each focus point is specified using the X and Y coordinates.

[0035] The microscope device 201 determines the Z coordinate when the LBC specimen 302 is in focus at each focus point, and uses the Z coordinates of each of the multiple focus points to generate a focal plane.

[0036] Figure 5 shows an example of the focal plane. In Figures 5(a) to 5(d), the horizontal axis represents the X or Y axis, and the vertical axis represents the Z axis. The black dots represent the Z coordinate when the LBC sample 302 is in focus at each focus point.

[0037] Figure 5(a) shows an example of a focal plane generated by calculating the average value of the Z coordinates. The microscope device 201 calculates the average value of the Z coordinates of each of the multiple focus points, as shown by the line 501, and determines the focal plane as a plane that passes through the point on the Z axis indicated by the average value and is parallel to the X and Y axes.

[0038] Figure 5(b) shows an example of a focal plane generated by planar approximation. The microscope device 201 determines the focal plane by performing planar approximation using the X, Y, and Z coordinates of each of the multiple focus points, as indicated by the line 502.

[0039] Figure 5(c) shows an example of a focal plane generated by surface approximation. The microscope device 201 determines the focal plane by performing surface approximation using the X, Y, and Z coordinates of each of the multiple focus points, as shown by curve 503.

[0040] Figure 5(d) shows an example of a focal plane generated by linear interpolation. The microscope device 201 determines the focal plane by performing linear interpolation using the X, Y, and Z coordinates of each of the multiple focus points, as shown by the broken line 504.

[0041] The Z step width represents the spacing between layers in the Z direction. The number of layers on the upper surface of the focus plane represents the number of layers above the focus plane, and the number of layers on the lower surface of the focus plane represents the number of layers below the focus plane. The microscope device 201 acquires an image of the LBC specimen 302 on the focus plane at each imaging position, acquires an image of the LBC specimen 302 with the number of layers on the upper surface of the focus plane above the focus plane at each imaging position, and acquires an image of the LBC specimen 302 with the number of layers on the lower surface of the focus plane below the focus plane at each imaging position.

[0042] The imaging range, focus point, Z step width, number of layers on the upper plane of focus, and number of layers on the lower plane of focus are examples of parameters used for imaging to acquire images of multiple types of specimens in multiple planes at different heights from the stage, each at multiple positions in a plane parallel to the stage.

[0043] For example, the number of upper layers on the focused surface of LBC specimens prepared by preparation method M2 is greater than the number of upper layers on the focused surface of LBC specimens prepared by preparation method M1. Furthermore, the number of lower layers on the focused surface of LBC specimens prepared by preparation method M2 is greater than the number of lower layers on the focused surface of LBC specimens prepared by preparation method M1.

[0044] The parameters used for imaging the tissue specimen include, for example, the imaging range and multiple focus points. The microscope device 201 generates a focal plane in the same manner as in the case of the LBC specimen 302 and acquires an image of the tissue specimen on the focal plane at each imaging position. The parameters used for imaging the tissue specimen are examples of predetermined parameters.

[0045] Figure 6 shows an example configuration of the microscope apparatus 201 of Figure 2. The microscope apparatus 201 of Figure 6 is an upright microscope and includes a control unit 611, a transport unit 612, a specimen storage unit 613, a focusing unit 614, a two-dimensional image sensor 615, a camera 616, a mirror 617, an imaging lens 618, and a splitter 619. The microscope apparatus 201 further includes a focusing device 620, an objective lens 621, a stage 622, a light source 623, an illumination optical system 624, and a mirror 625. These components are hardware.

[0046] The light source 623 emits light according to a control signal from the control unit 611. The illumination light from the light source 623 is reflected by the mirror 625 and then irradiated onto the slide glass 631 placed on the stage 622 via the illumination optical system 624. A specimen is coated or placed on the slide glass 631. The specimen on the slide glass 631 is an example of a specimen to be imaged.

[0047] The optical axis of the objective lens 621 represents the Z direction. The objective lens 621 moves in the Z direction by the operation of the focusing mechanism 620.

[0048] The stage 622 moves according to control signals from the control unit 611. The stage 622 moves at least in the X and Y directions perpendicular to the optical axis of the objective lens 621. The stage 622 may also move in the Z direction. The stage 622 may include actuators, including a stepping motor and a ball screw (not shown), and the position of the stage 622 may be controlled by controlling the actuators in an open-loop manner.

[0049] Light that has passed through the specimen on the slide glass 631 enters the splitter 619 via the objective lens 621. The splitter 619 splits the incident light into two, directing one beam to the imaging lens 618 and the other to the mirror 617. The light that has passed through the imaging lens 618 enters the two-dimensional image sensor 615, and the light reflected by the mirror 617 enters the focusing unit 614.

[0050] The two-dimensional image sensor 615 acquires an image of the specimen on the slide glass 631 by imaging it according to the control signal from the control unit 611, and outputs the acquired image to the control unit 611. The two-dimensional image sensor 615 may be a CMOS (Complementary Metal-Oxide-Semiconductor) image sensor.

[0051] The focusing device 620 changes the distance between the objective lens 621 and the stage 622. The focusing device 620 moves the objective lens 621 in the Z direction according to a control signal from the control unit 611. The focusing unit 614 detects the focus position in the Z direction from the incident light, for example, using the optical path length difference method, and outputs focus evaluation information indicating the detected focus position to the control unit 611.

[0052] The control unit 611 uses the focus evaluation information to determine whether to move the objective lens 621 upward or downward, and controls the focusing device 620. As a result, the focusing device 620 moves the objective lens 621 in the Z direction to focus on the specimen on the slide glass 631. The control unit 611 can determine whether to move the objective lens 621 upward or downward using, for example, the control method described in Patent Document 3.

[0053] The specimen storage unit 613 stores one or more slides 631. The transport unit 612 transports one of the slides 631 from the specimen storage unit 613 to the stage 622 according to a control signal from the control unit 611.

[0054] Figure 7 shows an example of the specimen storage section 613 of Figure 6. The specimen storage section 613 of Figure 7 has insertion slots 711-1 to 711-5. Insertion slots 711-i (i=1 to 5) are examples of storage sections. The number of insertion slots 711-i may be 4 or less, or 6 or more.

[0055] The user places one or more glass slides 631 into the rack 712 and inserts the rack 712 into one of the insertion slots 711-i. The control unit 611 controls the transport unit 612 to transport each glass slide 631 from the rack 712 inserted into the insertion slots 711-i to the stage 622.

[0056] The camera 616 acquires a macro image of the slide glass 631 placed on the stage 622 by imaging it according to a control signal from the control unit 611. The camera 616 then outputs the acquired macro image to the control unit 611. The camera 616 is an example of an imaging device that acquires a macro image of a specimen to be imaged.

[0057] The control unit 611 controls the transport unit 612, the specimen storage unit 613, the focusing unit 614, the two-dimensional image sensor 615, the camera 616, the focusing device 620, the stage 622, and the light source 623. The control unit 611 receives specific parameters from the control device 202 and scans the specimen on the slide glass 631 by controlling the focusing unit 614, the two-dimensional image sensor 615, the focusing device 620, and the stage 622 according to the received parameters.

[0058] For example, if the specimen is a tissue specimen, the control unit 611 controls the focusing device 620 to move the objective lens 621 in the Z direction so that it is in focus on the specimen at each focus point included in the parameters. The control unit 611 then determines the Z coordinate when the specimen is in focus at each focus point and generates a focal plane using the Z coordinates of each of the multiple focus points, as shown in Figure 5.

[0059] Next, the control unit 611 moves the stage 622 in the X and Y directions to cover the imaging range included in the parameters, causing the two-dimensional image sensor 615 to image the specimen on the slide glass 631 along the focal plane. As a result, the control unit 611 acquires multiple images covering the imaging range and outputs them to the image processing device 203.

[0060] If the specimen is an LBC specimen, the control unit 611 generates a focal plane in the same manner as in the case of a tissue specimen. Next, the control unit 611 moves the stage 622 in the X and Y directions to cover the imaging range included in the parameters, causing the two-dimensional image sensor 615 to image the specimen on the slide glass 631.

[0061] At this time, the control unit 611 controls the focusing device 620 to move the objective lens 621 in the Z direction so that images of multiple planes having intervals indicated by the Z step width are acquired at each imaging position on the specimen. The images of the multiple planes include an image on the focusing plane at each imaging position, an image of a plane with a number of layers on the upper surface of the focusing plane above the focusing plane, and an image of a plane with a number of layers on the lower surface of the focusing plane below the focusing plane.

[0062] As a result, the control unit 611 acquires images of the in-focus plane at each imaging position, images of the upper surface layer number at each imaging position, and images of the lower surface layer number at each imaging position, and outputs them to the image processing device 203.

[0063] Figure 8 shows an example of the functional configuration of the control device 202 in Figure 2. The control device 202 in Figure 8 includes a selection unit 811, a display unit 812, a communication unit 813, and a storage unit 814.

[0064] The memory unit 814 stores setting information 821 that includes multiple parameters. Each parameter is used for imaging each of several types of specimens and is pre-set according to each type of specimen. In the setting information 821, the multiple parameters are associated with each of several types. The setting information 821 is an example of parameter mapping information that associates each of several types with the parameters used for imaging each of several types of specimens.

[0065] The communication unit 813 communicates with the microscope device 201 via the communication network 204. The selection unit 811 selects specific parameters from among multiple parameters included in the setting information 821 according to the type of specimen on the slide glass 631, and outputs the specific parameters to the microscope device 201 via the communication unit 813. The display unit 812 displays the parameter selection screen according to the instructions from the selection unit 811.

[0066] The selection unit 811 can select a specific parameter using, for example, any of the selection methods P1 to P5.

[0067] In selection method P1, the selection unit 811 displays the parameter selection screen on the display unit 812. The parameter selection screen includes parameter identification information indicating each of the multiple parameters included in the setting information 821. The selection unit 811 selects the parameter indicated by the specific parameter identification information selected by the user from among the parameter identification information included in the parameter selection screen as the specific parameter.

[0068] Figure 9 is a flowchart showing an example of the first control process using selection method P1. In the case of selection method P1, as shown in Figure 7, the user places one or more slides 631 in the rack 712 and inserts the rack 712 into one of the insertion slots 711-i. The control unit 611 of the microscope apparatus 201 acquires identification information indicating the specimen on each slide 631 in the rack 712 inserted into the insertion slot 711-i and outputs it to the control device 202.

[0069] The selection unit 811 receives specimen IDs from the microscope device 201 via the communication unit 813, which indicate the specimens on each slide glass 631 in the rack 712 (step 901). The specimen ID is identification information that indicates the specimen on the slide glass 631. The selection unit 811 then displays a parameter selection screen including the received specimen ID on the display unit 812 (step 902).

[0070] Figure 10 shows an example of the parameter selection screen. In Figure 10, S1, S2, and S3 correspond to the specimen ID indicating the specimen on the slide glass 631, and T, M1, and M2 correspond to parameter identification information indicating the parameters. T indicates the parameters of the tissue specimen, M1 indicates the parameters of the LBC specimen prepared by preparation method M1, and M2 indicates the parameters of the LBC specimen prepared by preparation method M2.

[0071] The user selects one of the parameter identification information from T, M1, or M2 for each sample ID. In the example in Figure 10, M1 is selected for S1 and S2, and M2 is selected for S3.

[0072] The selection unit 811 selects from among multiple parameters included in the setting information 821 the parameter indicated by the parameter identification information selected for each specimen ID as the specific parameter for the specimen indicated by that specimen ID (step 903). Then, the selection unit 811 outputs the parameter for each specimen ID to the microscope device 201 via the communication unit 813 (step 904).

[0073] Each time a slide glass 631 in the rack 712 is transported to the stage 622, the control unit 611 of the microscope apparatus 201 selects the parameter for the specimen ID that indicates the specimen on that slide glass 631 from among the parameters for each specimen ID. Then, using the selected parameter, the control unit 611 controls the focusing unit 614, the two-dimensional image sensor 615, the focusing device 620, and the stage 622 to acquire multiple images of the specimen (step 905).

[0074] In selection methods P2 to P4, the selection unit 811 identifies the type of specimen on the slide glass 631 from the information captured in the macro image of the slide glass 631, and uses the setting information 821 to select the parameter corresponding to the specimen type as a specific parameter.

[0075] In selection method P2, the information captured in the macro image is, for example, the string 304 shown in Figure 3(a), and the string 304 represents the type of sample. The selection unit 811 identifies the type of sample by performing character recognition on the string captured in the macro image.

[0076] Figure 11 is a flowchart showing an example of a second control process using selection method P2. In the case of selection method P2, the control unit 611 of the microscope apparatus 201 acquires a macro image of the slide glass 631 by having the camera 616 image the slide glass 631 on the stage 622, and outputs it to the control device 202.

[0077] The selection unit 811 receives a macro image from the microscope device 201 via the communication unit 813 (step 1101), and identifies the type of specimen by performing character recognition on the string of characters shown in the macro image (step 1102).

[0078] Next, the selection unit 811 selects a parameter corresponding to the identified specimen type from among the multiple parameters included in the setting information 821 as a specific parameter for the specimen on the slide glass 631 (step 1103). Then, the selection unit 811 outputs the specific parameter to the microscope device 201 via the communication unit 813 (step 1104).

[0079] The control unit 611 of the microscope apparatus 201 acquires multiple images of the specimen by controlling the focusing unit 614, the two-dimensional image sensor 615, the focusing device 620, and the stage 622 using parameters received from the control device 202 (step 1105).

[0080] In selection method P3, the information captured in the macro image is, for example, the two-dimensional code 306 shown in Figure 3(b), and the two-dimensional code 306 represents the type of specimen. The selection unit 811 identifies the type of specimen by reading the two-dimensional code captured in the macro image. The information captured in the macro image may also be a barcode representing the type of specimen.

[0081] Figure 12 is a flowchart showing an example of a third control process using selection method P3. In the case of selection method P3, the control unit 611 of the microscope apparatus 201 acquires a macro image of the slide glass 631 by having the camera 616 image the slide glass 631 on the stage 622, and outputs it to the control device 202.

[0082] The selection unit 811 receives a macro image from the microscope device 201 via the communication unit 813 (step 1201), and identifies the type of specimen by reading the two-dimensional code shown in the macro image (step 1202).

[0083] Next, the selection unit 811 selects from among the multiple parameters included in the setting information 821 the parameter corresponding to the identified specimen type as the specific parameter for the specimen on the slide glass 631 (step 1203). Then, the selection unit 811 outputs the specific parameter to the microscope device 201 via the communication unit 813 (step 1204).

[0084] The control unit 611 of the microscope apparatus 201 acquires multiple images of the specimen by controlling the focusing unit 614, the two-dimensional image sensor 615, the focusing device 620, and the stage 622 using parameters received from the control device 202 (step 1205).

[0085] In selection method P4, the information captured in the macro image is, for example, the two-dimensional code 306 shown in Figure 3(b), and the two-dimensional code 306 represents the sample ID of the sample. The storage unit 814 further stores type correspondence information that associates the sample ID of each of the multiple types with each of the multiple types.

[0086] The selection unit 811 identifies the specimen ID of a specimen by reading the two-dimensional code captured in the macro image, and uses the type correspondence information to identify the type of specimen corresponding to the identified specimen ID. The information captured in the macro image may be a barcode representing the specimen ID of the specimen.

[0087] Figure 13 is a flowchart showing an example of a fourth control process using selection method P4. In the case of selection method P4, the control unit 611 of the microscope apparatus 201 acquires a macro image of the slide glass 631 by having the camera 616 image the slide glass 631 on the stage 622, and outputs it to the control device 202.

[0088] The selection unit 811 receives a macro image from the microscope device 201 via the communication unit 813 (step 1301). The selection unit 811 then reads the two-dimensional code in the macro image to identify the specimen ID of the specimen (step 1302), and uses the type correspondence information to identify the type of specimen corresponding to the identified specimen ID (step 1303).

[0089] Next, the selection unit 811 selects from among the multiple parameters included in the setting information 821 the parameter corresponding to the identified specimen type as the specific parameter for the specimen on the slide glass 631 (step 1304). Then, the selection unit 811 outputs the specific parameter to the microscope device 201 via the communication unit 813 (step 1305).

[0090] The control unit 611 of the microscope apparatus 201 acquires multiple images of the specimen by controlling the focusing unit 614, the two-dimensional image sensor 615, the focusing device 620, and the stage 622 using parameters received from the control device 202 (step 1306).

[0091] Instead of the memory unit 814 storing the type mapping information, a database (not shown) may store the type mapping information. If the database stores the type mapping information, in step 1303, the selection unit 811 outputs the identified sample ID to the database via the communication unit 813 and receives the sample type corresponding to that sample ID from the database.

[0092] In selection method P5, the memory unit 814 stores alternative setting information R instead of setting information 821. In setting information R, multiple parameters are associated with multiple insertion slots 711-i of the specimen storage unit 613. Setting information R is an example of parameter mapping information that associates the parameters used for imaging each of the multiple storage units with each of the multiple types of specimens.

[0093] The user places one or more slides 631 of the same type into the rack 712 and inserts the rack 712 into a specific slot 711-i corresponding to the type of specimen on the slide 631.

[0094] The control unit 611 of the microscope apparatus 201 controls the transport unit 612 to transport any of the slide glasses 631 from the rack 712 inserted into a specific insertion slot 711-i to the stage 622. The control unit 611 then obtains a specific insertion slot ID indicating the specific insertion slot 711-i and outputs it to the control device 202. The insertion slot ID is identification information indicating the insertion slot 711-i. The selection unit 811 uses the setting information R to select the parameter corresponding to the specific insertion slot 711-i indicated by the specific insertion slot ID as the specific parameter.

[0095] Figure 14 is a flowchart showing an example of a fifth control process using selection method P5. First, the selection unit 811 receives a specific insertion slot ID from the microscope device 201 via the communication unit 813 (step 1401).

[0096] Next, the selection unit 811 selects a parameter corresponding to the received insertion slot ID from among several parameters included in the setting information R, as a specific parameter for the specimen on the slide glass 631 transported to the stage 622 (step 1402). Then, the selection unit 811 outputs the specific parameter to the microscope device 201 via the communication unit 813 (step 1403).

[0097] The control unit 611 of the microscope apparatus 201 acquires multiple images of the specimen by controlling the focusing unit 614, the two-dimensional image sensor 615, the focusing device 620, and the stage 622 using parameters received from the control device 202 (step 1404).

[0098] According to the microscope system in Figure 2, the image acquisition parameters for the specimen are set according to the type of specimen. Specifically, if the specimen is an LBC specimen, the XY and Z ranges are set according to the preparation method, and if the specimen is a tissue specimen, the Z direction is set to only one focal plane.

[0099] For example, if the specimen is a LBC specimen, the parameters used for imaging in multiple planes at different heights from the stage 622 of the microscope device 201 are set to match the LBC specimen on the stage 622. This eliminates the need for the user to change the parameter settings for generating the Z-stack image each time the LBC specimen being imaged is replaced. Therefore, images of the specimen in multiple planes at different heights from the stage 622 can be acquired efficiently.

[0100] Even when LBC specimens and tissue specimens are mixed as specimens stored in the specimen storage unit 613, the complexity of setting image acquisition parameters is reduced, and images can be acquired efficiently.

[0101] According to selection methods P2 to P5, the parameters used for imaging the specimen on the slide glass 631 are automatically selected, eliminating the need for the user to select parameters for each specimen. Therefore, the user's workload is reduced.

[0102] Instead of providing the microscope device 201, control device 202, and image processing device 203 separately, the microscope device 201 may combine the functions of either the control device 202 or the image processing device 203. Alternatively, the microscope device 201 may combine the functions of both the control device 202 and the image processing device 203, or the control device 202 may combine the functions of the image processing device 203.

[0103] Incidentally, when the specimen is an LBC specimen, there will be some variation in the coating area on the slide glass 631 for each specimen. For this reason, it is desirable to adjust the imaging range included in the parameters to match the coating area of ​​each specimen. In this case, the selection unit 811 may correct the imaging range included in the parameters based on the range of the specimen captured in the macro image.

[0104] For example, as shown in Figures 3(a) and 3(b), if the shape of the coating area is circular, the selection unit 811 calculates the X and Y coordinates of the center position of the circle representing the range of the specimen captured in the macro image. Then, without changing the size of the circle representing the imaging range, the selection unit 811 corrects the imaging range by replacing the X and Y coordinates of the center position with the calculated X and Y coordinates. The focus point, Z step width, number of upper and lower layers of the focusing plane included in the parameters are not changed.

[0105] By correcting the imaging range included in the parameters based on the extent of the specimen captured in the macro image, the user no longer needs to adjust the imaging range for each specimen. Therefore, the user's workload is reduced.

[0106] Figure 15 is a flowchart showing an example of a correction process for correcting the imaging range. The control unit 611 of the microscope apparatus 201 causes the camera 616 to image the slide glass 631 on the stage 622, thereby acquiring a macro image of the slide glass 631 and outputting it to the control device 202.

[0107] The selection unit 811 receives a macro image from the microscope device 201 via the communication unit 813 (step 1501), and identifies the range of the specimen shown in the macro image by image recognition (step 1502).

[0108] Next, the selection unit 811 corrects the imaging range included in the specific parameter selected using one of the selection methods P1 to P5 to match the range of the specified specimen (step 1503). Then, the selection unit 811 outputs the specific parameter, including the corrected imaging range, to the microscope device 201 via the communication unit 813 (step 1504).

[0109] The control unit 611 of the microscope apparatus 201 acquires multiple images of the specimen by controlling the focusing unit 614, the two-dimensional image sensor 615, the focusing device 620, and the stage 622 using parameters received from the control device 202 (step 1505).

[0110] The configuration of the microscope system shown in Figure 2 is merely an example, and some components may be omitted or modified depending on the application or conditions of the microscope system.

[0111] The configuration of the microscope apparatus 201 in Figure 6 is merely an example, and some components may be omitted or modified depending on the application or conditions of the microscope system. For example, the microscope apparatus 201 may be an inverted microscope. The microscope apparatus 201 may detect the focus position using an image plane phase difference method instead of an optical path length difference method. When identifying the type of specimen to be imaged, a reading device such as a barcode reader that reads information for identifying the type of specimen may be provided separately from the macro camera. In this case, instead of using the information captured in the macro image, the type of specimen to be imaged is identified using the information read by the reading device.

[0112] The configuration of the specimen storage unit 613 in Figure 7 is merely an example, and some components may be omitted or changed depending on the configuration or conditions of the microscope device 201.

[0113] The configuration of the control device 202 in Figure 8 is merely an example, and some components may be omitted or changed depending on the application or conditions of the microscope system. For example, if any of selection methods P2 to P5 is used, the display unit 812 can be omitted.

[0114] The LBC specimen shown in Figure 1 is merely an example; LBC specimens vary depending on the specimen collected from the patient and the preparation method. The specimen to be imaged may also be a substance other than the specimen. Substances other than the specimen may include substances collected from the atmosphere, water, soil, or space, or artificially synthesized substances.

[0115] The labels shown in Figures 3(a) and 3(b) are merely examples, and the labels attached to the slide glass will vary depending on the application or conditions of the microscope system. The focus points shown in Figure 4 are merely examples, and the focus points included in the parameters will vary depending on the application or conditions of the microscope system. The in-focus planes shown in Figures 5(a) to 5(d) are merely examples, and the in-focus planes may be generated by other methods. The parameter selection screen shown in Figure 10 is merely an example, and the display unit 812 may display a parameter selection screen in a different form.

[0116] The flowcharts in Figures 9 and 11-15 are merely examples, and some processes may be omitted or modified depending on the configuration or conditions of the microscope system.

[0117] Figure 16 shows an example of the hardware configuration of the first information processing device used as the control unit 611 in Figure 6. The information processing device in Figure 16 includes a CPU (Central Processing Unit) 1601, memory 1602, auxiliary storage device 1603, and interface 1604. These components are hardware and are connected to each other by a bus 1605.

[0118] Memory 1602 is a semiconductor memory such as ROM (Read Only Memory) or RAM (Random Access Memory), and stores the program and data used for processing.

[0119] The CPU 1601 (processor) performs the processing of the control unit 611, for example, by executing a program using the memory 1602.

[0120] The auxiliary storage device 1603 is, for example, a magnetic disk drive, an optical disk drive, a magneto-optical disk drive, a tape drive, etc. The auxiliary storage device 1603 may also be a hard disk drive or an SSD (Solid State Drive). The information processing device can store programs and data in the auxiliary storage device 1603 and load them into the memory 1602 for use.

[0121] Interface 1604 is a communication device that is connected to a communication line or the like and performs data conversion associated with communication.

[0122] The control unit 611 communicates with the transport unit 612, the specimen storage unit 613, the focusing unit 614, the two-dimensional image sensor 615, the camera 616, the focusing device 620, the stage 622, and the light source 623 via the interface 1604. The control unit 611 also communicates with the control device 202 and the image processing device 203 via the interface 1604.

[0123] As the image processing device 203 in Figure 2, the same information processing device as in Figure 16 can be used.

[0124] Figure 17 shows an example of the hardware configuration of a second information processing device used as the control device 202 in Figure 8. The information processing device in Figure 17 includes a CPU 1701, memory 1702, input device 1703, output device 1704, auxiliary storage device 1705, media drive device 1706, and network connection device 1707. These components are hardware and are connected to each other by a bus 1708.

[0125] Memory 1702 is, for example, a semiconductor memory such as ROM or RAM, and stores the program and data used for processing. Memory 1702 may also operate as the storage unit 814 in Figure 8.

[0126] The CPU 1701 operates as the selection unit 811 in Figure 8, for example, by executing a program using the memory 1702.

[0127] The input device 1703 is, for example, a keyboard, a pointing device, etc., and is used for inputting instructions or information from the user. The output device 1704 is, for example, a display device, a printer, a speaker, etc., and is used for querying or giving instructions to the user and outputting processing results. The output device 1704 may also operate as the display unit 812 in Figure 8. The query may be a parameter selection screen.

[0128] The auxiliary storage device 1705 is, for example, a magnetic disk drive, an optical disk drive, a magneto-optical disk drive, a tape drive, or a flash memory. The auxiliary storage device 1705 may also be a hard disk drive or an SSD. The information processing device can store programs and data in the auxiliary storage device 1705 and load them into the memory 1702 for use. The auxiliary storage device 1705 may also operate as the storage unit 814 in Figure 8.

[0129] The media drive unit 1706 drives the portable recording medium 1709 and accesses its recorded contents. The portable recording medium 1709 can be a memory device, a flexible disk, an optical disk, a magneto-optical disk, etc. The portable recording medium 1709 may also be a CD-ROM (Compact Disk Read Only Memory), a DVD (Digital Versatile Disk), a USB (Universal Serial Bus) memory, etc. The user can store programs and data on the portable recording medium 1709 and load them into the memory 1702 for use.

[0130] Thus, the computer-readable recording medium that stores the programs and data used in the processing is a physical (non-temporary) recording medium such as memory 1702, auxiliary storage device 1705, or portable recording medium 1709.

[0131] The network connection device 1707 is a communication device connected to the communication network 204 and performs data conversion associated with communication. The information processing device can receive programs and data from external devices via the network connection device 1707 and load them into memory 1702 for use. The network connection device 1707 may also operate as the communication unit 813 in Figure 8.

[0132] Note that the information processing device does not need to include all the components shown in Figure 17, and some components may be omitted depending on the application or conditions. For example, if a user interface is not required, the input device 1703 and output device 1704 may be omitted. If the portable recording medium 1709 is not used, the media drive device 1706 may be omitted.

[0133] While embodiments of the disclosure and their advantages have been described in detail, those skilled in the art will be able to make various modifications, additions, and omissions without departing from the scope of the invention as expressly stated in the claims. [Explanation of Symbols]

[0134] 101, 301, 631 microscope slides 102 cells 103 Focal plane 201 Microscope equipment 202 Control Unit 203 Image Processing Device 204 Communication Network 302 LBC specimen Labels 303 and 305 304 string 306 2D code 401 Imaging range 501, 502 straight line 503 curve 504 Linear graph 611 Control Unit 612 Conveying Unit 613 Specimen storage section 614 Focusing section 615 2D image sensor 616 Camera 617, 625 Miller 618 Imaging lens 619 Splitter 620 Focusing device 621 Objective lens 622 stages 623 Light source 624 Illumination optical system 711-1~711-5 Insertion slot 712 racks 811 Selection Section 812 Display section 813 Communications Department 814 Storage section 821 Configuration Information 1601, 1701 CPU 1602, 1702 memory 1603, 1705 Auxiliary storage device 1604 Interface 16:05, 17:08 Bus 1703 Input device 1704 Output device 1706 Media drive device 1707 Network Connection Device 1709 Portable recording media

Claims

1. The objective lens, The stage and, A two-dimensional image sensor for imaging the target specimen on the aforementioned stage, A focusing device that changes the distance between the objective lens and the stage, A control unit acquires specific parameters used for imaging the target specimen, selected from among the parameters used for imaging each of multiple types of specimens according to the type of specimen to be imaged, and controls the stage, the two-dimensional image sensor, and the focusing device based on the specific parameters to acquire images of the target specimen in each of multiple planes at different heights from the stage, at each of multiple positions in a plane parallel to the stage. Equipped with, A microscope system characterized in that the parameters used for imaging each of the plurality of types of specimens include parameters used for imaging to acquire images of each of the plurality of types of specimens in each of the plurality of planes at each of the plurality of locations.

2. A storage unit that stores parameters used for imaging each of the aforementioned multiple types of specimens, A selection unit that selects a specific parameter from among the parameters used for imaging each of the multiple types of specimens, according to the type of specimen to be imaged, and outputs the specific parameter to the control unit, Display unit and Furthermore, The microscope system according to claim 1, characterized in that the selection unit displays parameter identification information on the display unit indicating parameters used for imaging each of the plurality of types of specimens, and selects a parameter indicated by a specific parameter identification information selected by the user from among the parameter identification information of each of the plurality of types of specimens as the specific parameter.

3. A storage unit that stores parameter correspondence information relating each of the aforementioned plurality of types to the parameters used for imaging each of the aforementioned plurality of types, A selection unit that selects a specific parameter from among the parameters used for imaging each of the multiple types of specimens, according to the type of specimen to be imaged, and outputs the specific parameter to the control unit, An imaging device that acquires macro images of the specimen to be imaged, Furthermore, The microscope system according to claim 1, characterized in that the selection unit identifies the type of specimen to be imaged from the information captured in the macro image, and uses the parameter correspondence information to select the parameter corresponding to the type of specimen to be imaged as the specific parameter.

4. The information captured in the macro image is a string of characters indicating the type of specimen being imaged. The microscope system according to claim 3, characterized in that the selection unit identifies the type of specimen to be imaged by performing character recognition on the string.

5. The information captured in the aforementioned macro image is a code indicating the type of specimen being imaged. The microscope system according to claim 3, characterized in that the selection unit identifies the type of specimen to be imaged by reading the code.

6. The information captured in the macro image is a code indicating the identification information of the specimen being imaged. The microscope system according to claim 3, characterized in that the selection unit identifies the identification information of the specimen to be imaged by reading the code, and identifies the type of specimen to be imaged that corresponds to the identification information of the specimen to be imaged using type correspondence information that associates the identification information of each of the multiple types of specimens with each of the multiple types.

7. A storage unit that stores parameter correspondence information relating each of the aforementioned plurality of types to the parameters used for imaging each of the aforementioned plurality of types, A selection unit that selects a specific parameter from among the parameters used for imaging each of the multiple types of specimens, according to the type of specimen to be imaged, and outputs the specific parameter to the control unit, A reading device that acquires information to identify the type of specimen to be imaged, Furthermore, The microscope system according to claim 1, characterized in that the selection unit identifies the type of specimen to be imaged from the information read by the reading device, and uses the parameter correspondence information to select the parameter corresponding to the type of specimen to be imaged as the specific parameter.

8. The information read by the reading device is a string of characters indicating the type of the specimen to be imaged. The microscope system according to claim 7, characterized in that the selection unit identifies the type of specimen to be imaged by performing character recognition on the string.

9. The information read by the aforementioned reading device is a code indicating the type of specimen to be imaged, The microscope system according to claim 7, characterized in that the selection unit identifies the type of specimen to be imaged by reading the code.

10. The information read by the reading device is a code indicating the identification information of the specimen to be imaged, The microscope system according to claim 7, characterized in that the selection unit identifies the identification information of the specimen to be imaged by reading the code, and identifies the type of specimen to be imaged that corresponds to the identification information of the specimen to be imaged using type correspondence information that associates the identification information of each of the multiple types of specimens with each of the multiple types.

11. A specimen storage unit having multiple storage compartments, A transport unit that transports the specimen to be imaged from the specimen storage unit to the stage, A storage unit that stores parameter correspondence information relating each of the plurality of storage units to the parameters used for imaging each of the plurality of types of specimens, A selection unit that selects a specific parameter from among the parameters used for imaging each of the multiple types of specimens, according to the type of specimen to be imaged, and outputs the specific parameter to the control unit, Furthermore, The control unit controls the transport unit to transport the specimen to be imaged from a specific storage unit among the plurality of storage units that stores the specimen to be imaged to the stage. The microscope system according to claim 1, characterized in that the selection unit uses the parameter correspondence information to select the parameter corresponding to the specific storage unit as the specific parameter.

12. A storage unit that stores parameters used for imaging each of the aforementioned multiple types of specimens, A selection unit that selects a specific parameter from among the parameters used for imaging each of the multiple types of specimens, according to the type of specimen to be imaged, and outputs the specific parameter to the control unit, An imaging device that acquires macro images of the specimen to be imaged, Furthermore, The aforementioned specific parameter includes the imaging range of the image of the target specimen on the stage, The microscope system according to claim 1, characterized in that the selection unit corrects the imaging range based on the range of the target specimen captured in the macro image.

13. Each of the aforementioned multiple types of specimens is a liquid-based cytological specimen, The microscope system according to any one of claims 1 to 12, characterized in that the aforementioned plurality of types represent a plurality of methods for preparing the liquid-type cytological specimen.

14. The microscope system according to any one of claims 1 to 12, characterized in that, when the specimen to be imaged is of a predetermined type other than the plurality of types, the control unit acquires the predetermined parameters selected from the parameters used for imaging each of the plurality of types of specimens and the predetermined parameters used for imaging the predetermined type of specimen, according to the type of specimen to be imaged, and controls the stage, the two-dimensional image sensor, and the focusing device based on the predetermined parameters to acquire an image of the specimen to be imaged at each of the plurality of positions.

15. Each of the aforementioned multiple types of specimens is a liquid-based cytological specimen, The aforementioned specified type of specimen is a tissue specimen, The microscope system according to claim 14, characterized in that the aforementioned multiple types represent multiple methods for preparing the liquid-type cytological specimen.

16. A storage unit in a microscope device that stores parameters used for imaging various types of specimens, A selection unit that selects specific parameters used for imaging a particular specimen from among the parameters used for imaging each of the aforementioned multiple types of specimens, according to the type of specimen to be imaged on the stage, and outputs the specific parameters to the microscope device. Equipped with, The microscope apparatus controls the stage, a two-dimensional image sensor for imaging the target specimen, and a focusing device for changing the distance between the objective lens and the stage, based on the specific parameters, thereby acquiring images of the target specimen in each of a plurality of planes at different heights from the stage, at each of a plurality of positions in a plane parallel to the stage. The control device is characterized in that the parameters used for imaging each of the plurality of types of specimens include parameters used for imaging to acquire images of each of the plurality of types of specimens in each of the plurality of planes at each of the plurality of locations.

17. In a microscope, specific parameters used for imaging a particular specimen are acquired from among the parameters used for imaging each of several types of specimens, according to the type of specimen being imaged on the stage. Based on the aforementioned specific parameters, the stage, the two-dimensional image sensor for imaging the target specimen, and the focusing device for changing the distance between the objective lens and the stage are controlled to acquire images of the target specimen at each of several positions in a plane parallel to the stage, and at each of several planes with different heights from the stage. A control method characterized in that the parameters used for imaging each of the plurality of types of specimens include parameters used for imaging to acquire images of each of the plurality of types of specimens in each of the plurality of planes at each of the plurality of locations.

Images