JP2011102916A - Microscope system - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To capture images of many slide glasses in a short time. <P>SOLUTION: A microscope system 1 includes: a microscope device 4 having a stage 8 for mounting each slide 2 with a sample thereon and moving it horizontally, and also having a plurality of slide holders provided on the stage 8 and capable of mounting a plurality of slides 2 parallel to one another; an accommodating unit 3 for accommodating the slides 2 with samples thereon; at least one transfer arm 5 for transferring each slide 2 between the accommodating unit 3 and the slide holders of the microscope device 4; and a control unit 6 for conveying an unobserved slide 2 to an empty one of the slide holders from the accommodating unit 3 by the transfer arm 5 and controls the microscope device 4 and transfer arm 5 so that another slide 2 may be conveyed by the transfer arm 5 during the capture of an image of a sample on each slide 2. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to a microscope system.

  Conventionally, when a high-magnification objective lens is used, the observation range that can be observed at one time is limited to only a small part of the specimen, so the specimen image is divided into small sections in advance, and the portion of the specimen corresponding to each small section Is a so-called virtual slide microscope system that constructs an entire image of a specimen by taking a high-resolution image of the specimen using a high-magnification objective lens and pasting the specimen images corresponding to the obtained small sections together It is known (for example, refer to Patent Document 1).

  In such a virtual slide microscope system, since it takes time to acquire the entire image of the specimen mounted on one slide glass, the operator does not perform the image acquisition operation, but in the microscope system. An image is automatically acquired. In such automatic image acquisition, hundreds of slide glasses are prepared, and for example, the image acquisition is sequentially performed while the slide glass is automatically replaced unattended at night. (For example, refer to Patent Document 2).

  In the microscope system of Patent Document 2, the slide glass accommodated in the tray is taken out one by one and placed on the stage for high-field image photographing, and the entire sample image is photographed. It is supposed to take a photo with a microscope.

JP 2008-191427 A JP 2003-248176 A

  However, in the microscope system disclosed in Patent Document 2, when a slide glass that has been taken out of a single tray and has been photographed for the entire image and the microscope image is returned to the first tray, the tray and the high-field image There is no description about a method for reciprocating the slide glass between the photographing stage.

  In general, transfer means such as a robot arm that supplies a slide glass from a tray to a high-field image capturing stage takes out the slide glass that has been photographed and is placed on the high-field image capturing stage. Then, an unphotographed slide glass is taken out from the other storage unit and conveyed to the high-field image photographing stage, and the whole image is photographed. For this reason, during the conveyance of the photographed slide glass and the conveyance of the non-photographed slide glass, the entire image cannot be photographed and a waiting time occurs. As described above, when sequentially acquiring images while exchanging hundreds of slide glasses, this waiting time is accumulated, and it takes a lot of time to finish photographing all the slide glasses. There is an inconvenience.

  The present invention has been made in view of the above-described circumstances, and an object thereof is to provide a microscope system capable of acquiring images of a large number of slide glasses in a short time.

In order to achieve the above object, the present invention provides the following means.
A microscope system according to the present invention includes a stage on which a slide carrying a specimen is mounted and moved in the horizontal direction, and a plurality of slide holder portions that are provided on the stage and can mount a plurality of the slides in parallel. A microscope apparatus, a storage section that stores a plurality of slides on which a specimen is mounted, and at least one transfer arm that transfers the slide between the storage section and the slide holder section of the microscope apparatus And the transfer arm transfers the unobserved slide from the accommodating portion to any empty slide holder portion, and transfers the other slides during the acquisition of the image of the specimen on the slide. A control unit that controls the microscope apparatus and the transfer arm so as to be conveyed by the mounting arm.
In the microscope system, the image of the specimen may be acquired by the microscope apparatus.

  According to these microscope systems, an unobserved slide is transferred from the accommodating portion to any empty slide holder portion by the transfer arm, and another slide is transferred to the transfer arm while acquiring an image of the specimen on the slide. Therefore, it is possible to acquire images of a large number of slide glasses in a short time.

  Furthermore, in the microscope system, the control unit is configured to transfer another slide from another slide holder unit to the transfer arm during acquisition of an image of the specimen on the slide. The transfer arm may be controlled.

  According to this microscope system, an unobserved slide is transferred from the storage unit to any empty slide holder unit by the transfer arm, and another slide holder unit receives another image while acquiring an image of the specimen on the slide. Since the slide is configured to be transferred to the transfer arm, the time required for the reciprocating movement of the slide by the transfer arm between the storage portion and the slide holder portion does not need to be stacked for all the slides, and many sheets The image of the slide glass can be acquired in a short time.

  In the microscope system, an enlarged photographing optical system for magnifying and observing the specimen, and a macro photographing optical system for obtaining an entire image of the specimen, which are arranged in a movable range of the slide by the stage so as to face the slide. The acquisition of the image of the specimen may be imaging by the macro imaging optical system.

  According to this microscope system, from the storage unit that stores a plurality of slides, the transfer arm takes out any unobserved slide, and transfers it to an empty slide holder unit provided on the stage, The macro imaging optical system is operated to acquire the entire image of the specimen mounted on the slide. Then, the slide from which the entire image has been acquired is sent to the enlarged photographing optical system by the operation of the stage, and after the enlarged photographing of the specimen is performed, the slide is returned to the accommodating portion by the transfer arm.

  Since a plurality of slide holder portions are provided, other unobserved slides can be transferred to other empty slide holder portions before collecting the enlarged and observed slides. That is, the transfer arm does not need to collect the slide that has been magnified and observed in an empty state, and other unobserved slides can be transferred to the slide holder portion and recovered in an empty state. .

  Further, the transfer of the magnified and observed slide to the transfer arm is performed during acquisition of the entire image of the specimen on the other slide by the macro imaging optical system. Since the stage is stopped during the acquisition of the entire image, the removal operation from the slide holder portion by the transfer arm can be easily performed. The operation of returning the magnified and observed slide collected in the transfer arm to the accommodating portion and the operation of taking out another unobserved slide from the accommodating portion and moving it to the vicinity of the empty slide holder portion are the other specimens. It is possible to carry out the whole image taking, the reciprocating movement between the macro photographing optical system and the magnification photographing optical system, and the photographing of the enlarged image in the macro photographing optical system.

  That is, according to this microscope system, it is not necessary to stack the time required for the reciprocating movement of the slide by the transfer arm between the storage unit and the slide holder unit for all the slides. It can be done in a short time.

  In the above invention, the control unit places the slide obtained by acquiring the entire image of the specimen by the macro imaging optical system so as to face the magnification imaging optical system, and the slide that has been magnified and observed by the magnification imaging optical system. It is preferable to control the stage so that a slide holder portion different from the slide holder portion to be mounted is disposed to face the macro imaging optical system.

  By doing in this way, the transfer arm that has taken out the unobserved slide from the storage unit can transfer the unobserved slide to the slide holder unit that is disposed facing the macro imaging optical system. Immediately after that, the entire image can be acquired. That is, it is not necessary to move the macro observation optical system by the stage after the unobserved slide is transferred to the slide holder, and the moving time can be shortened. Therefore, it is possible to acquire images of a large number of slide glasses in a shorter time.

In the above invention, the control unit performs image processing on an entire image of the specimen acquired by the macro imaging optical system, specifies an observation region to be magnified, and magnifies the identified observation region. As described above, the stage may be controlled.
In this way, the number of enlarged images acquired by the magnification photographing optical system can be limited to the specified observation region, and the required time can be shortened.

  In the above invention, each slide is provided with a readable identification mark including identification information of the slide, a mark reading device for reading the identification mark, and the slide on which the identification mark and the identification mark are provided. A storage unit that stores the observation conditions of the specimen in association with each other, and the control unit reads out the observation conditions corresponding to the identification information included in the identification mark read by the label reading device from the storage unit. The microscope apparatus may be controlled.

  By doing in this way, prior to the observation of the sample mounted on the slide, the control unit reads the observation condition corresponding to the identification information included in the identification mark read by the label reading device, so that observation is performed for each sample. Without determining the conditions, an enlarged image of the specimen can be acquired under observation conditions suitable for the specimen observation in a short time.

  According to the present invention, there is an effect that images of a large number of slide glasses can be acquired in a short time.

1 is an overall configuration diagram showing a microscope system according to an embodiment of the present invention. It is a front view which shows the microscope apparatus with which the microscope system of FIG. 1 is equipped. It is a flowchart explaining the operation | movement of the transfer arm in the microscope system of FIG. 2 is a flowchart for explaining the operation of the microscope apparatus in the microscope system of FIG. It is a flowchart explaining operation | movement of the control part in the microscope system of FIG. It is a figure explaining supply and taking-out of the slide in the slide holder part with which the microscope apparatus of the microscope system of Drawing 1 was equipped, (a) At the time of supply of an unobserved slide, (b) At the end of observation of a slide, (c ) Shows the positional relationship between the slide holder and the macro photographing optical system when taking out the observed slide.

A microscope system 1 according to an embodiment of the present invention will be described below with reference to the drawings.
As shown in FIG. 1, the microscope system 1 according to the present embodiment includes a rack (accommodating portion) 3 that accommodates a large number of slides 2 on which a specimen A to be observed (see FIG. 6) is mounted, A microscope apparatus 4 that acquires an entire image and an enlarged image of the specimen A on the slide 2 accommodated in the rack 3, and a transfer arm 5 that conveys and transfers the slide 2 between the rack 3 and the microscope apparatus 4. And a control unit 6 for controlling them.

The slide 2 is made of a transparent flat plate material (for example, glass), the specimen A is mounted on the surface thereof, and a barcode (identification mark) 7 including identification information for identifying each specimen A is affixed. ing. The bar code 7 includes identification information for identifying the sample A mounted on the slide 2.
The rack 3 includes, for example, a plurality of storage chambers that are two-dimensionally arranged in the vertical direction (vertical direction) and the horizontal direction, and is stored in each storage chamber one by one with the end of the slide 2 protruding. It is like that.

  As shown in FIG. 2, the microscope apparatus 4 includes a stage 8 that can move at least two-dimensionally in the horizontal direction, and a macro imaging optical system that acquires an entire image of the specimen A on the slide 2 mounted on the stage 8. 9, an enlarged photographing optical system 10 for acquiring an enlarged image of the specimen A, and a barcode reader 11 for reading the barcode 7 attached to the slide 2. The position of the macro photographing optical system 9 is fixed. Further, the barcode reader 11 is located at a position where the barcode 7 attached to the slide 2 can be read when the entire image of the specimen A on the slide 2 is photographed by the macro photographing optical system 9, for example. It is fixed.

  As shown in FIG. 6, a slide holder 12 capable of fixing two slides 2 in parallel is attached to the stage 8. The slide holder 12 is provided with a first slide holder portion 12b and a second slide holder portion 12c at two locations. Each slide holder portion 12b, 12c has a through portion 12a penetrating in the vertical direction (vertical direction), and each slide 2 is held horizontally by the peripheral portion of the slide 2.

The stage 8 has a horizontal movable range in which the slide 2 can be horizontally moved to a position where the entire specimen A can be observed by both the macro photographing optical system 9 and the magnification photographing optical system 10. .
The macro photographing optical system 9 and the magnification photographing optical system 10 have optical axes C1 and C2 arranged in the vertical direction, respectively.

The macro photographing optical system 9 includes an illumination optical system 9a disposed below the stage 8, an objective lens 9b disposed above the stage 8, and a macro image sensor 9c.
The magnification photographing optical system 10 includes an epi-illumination optical system 10A that irradiates illumination light from above the stage 8, a transmission illumination optical system 10B that irradiates illumination light from below the stage 8, and an objective disposed above the stage 8. A lens 10a and a micro imaging device 10b are provided.

  In the figure, reference numerals 10c and 10d are light sources, reference numeral 10e is a mirror, reference numeral 10f is a dichroic mirror, and reference numeral 10g is an eyepiece optical system. In FIG. 2, the display of optical elements such as lenses and filters is omitted.

  The transfer arm 5 includes a grip portion 5a that releasably grips one slide 2 and a moving mechanism 5b that can move the grip portion 5a in a three-dimensional manner. The moving mechanism 5b is operated, the end of the slide 2 accommodated in the rack 3 is gripped by the gripping portion 5a, and the moving mechanism 5b is operated to slide the slide 2 on the slide holder 12 on the stage 8. It conveys to the parts 12b and 12c.

The control unit 6 includes a storage unit 6a that stores the identification information of the slide 2 and the observation conditions in association with each other. Observation conditions include an observation method for epi-illumination observation or transmission observation, the wavelength and intensity of the excitation light source to be used, the wavelength of fluorescence to be acquired, and the like.
The storage unit 6a stores the entire image acquired by the macro imaging optical system 9 and the enlarged image acquired by the enlarged imaging optical system 10 in association with the identification information.

Further, the control unit 6 controls the microscope apparatus 4 and the transfer arm 5 as follows.
First, for the transfer arm 5, as shown in FIG. 3, the slides 2 are taken out from the rack 3 one by one in a predetermined order (step S1), and the slide holder part 12b or the slide holder part is taken out. The transfer arm 5 is instructed to carry it to 12c (slide holder part 12b in this embodiment) (step S2).
In addition, the slide 2 transported from the rack 3 is transported to the transfer arm 5 to a nearby position where it can be transported to the slide holder portion 12b, and waits on the spot (step S3).

For the microscope apparatus 4, as shown in FIG. 4, the stage 8 is moved until one of the empty slide holder portions 12b is arranged on the optical axis C1 of the macro photographing optical system 9. (Step S11) is instructed.
Then, in the state in which the slide holder portion 12b is disposed on the optical axis C1 of the macro photographing optical system 9, the macro photographing optical system moves the slide 2 held by the grasping portion 5a with respect to the transfer arm 5 that has been waiting. 9 is instructed to be transferred to the slide holder portion 12b disposed on the optical axis C1 (step S4). As a result, as shown in FIG. 6A, the unobserved slide 2 (the slide 2 shown by the solid line in FIG. 6A) is held by the slide holder portion 12b at a position below the macro photographing optical system 9. Is done.

  Next, as shown in FIG. 4, the control unit 6 confirms that the slide 2 has been transferred (step S <b> 12), and the barcode 7 on the slide 2 by the barcode reader 11 of the microscope apparatus 4 is checked. Reading (step S13) and acquisition of the entire image of the specimen A on the slide 2 by the macro photographing optical system 9 (step S14), that is, macro photographing are performed.

  At the same time, as shown in FIG. 3, the control unit 6 checks whether or not there is the observed slide 2 in the other slide holder unit 12c (step S5). An instruction is given to take out the observed slide 2 from the slide holder portion 12c by the mounting arm 5 (step S6) and return it to the rack 3 (step S7). Thus, as shown in FIG. 6A, when there is an observed slide 2 (slide 2 shown by a two-dot chain line in FIG. 6A), the slide 2 is taken out from the other slide holder portion 12c and rack Returned to 3. When the observed slide 2 does not exist in the other slide holder portion 12c, the transfer arm 5 is instructed to take out the slide 2 to be observed next from the rack 3. Then, it is confirmed whether or not the observation of all the slides 2 in the rack 3 is completed (step S8), and the process is repeated from step S1 until the observation is completed.

When the barcode 7 is read, the control unit 6 searches the observation condition in the storage unit 6a based on the identification information included in the barcode 7 as shown in FIG. 5 (step S21). The microscope apparatus 4 is instructed to change the setting (step S22).
Further, when the entire image is acquired by the macro imaging optical system 9, the control unit 6 moves the slide 2 from the optical axis C1 of the macro imaging optical system 9 with respect to the microscope apparatus 4 as shown in FIG. An instruction is given to move the stage 8 so as to be placed on the optical axis C2 of the magnifying optical system 10 (step S15).

  At the same time, the control unit 6 confirms that the entire image has been acquired (step S23), and determines the area in which the acquired entire image is subjected to image processing and magnified observation, the acquisition order and the number of acquired images. It is set (step S24). For example, when the specimen A includes a living cell, the region is set such that the region where the living cell exists and the region where the living cell does not exist are determined, and the observation region is set only for the existing region.

  When it is confirmed that the observation area or the like has been set (step S16) and the slide 2 is placed on the optical axis C2 of the magnifying optical system 10, the microscope apparatus 4 obtains the acquisition set in the set acquisition order. The number of enlarged images is acquired sequentially (step S17). During the micro-photographing by the microscope apparatus 4, the observed slide 2 is conveyed by the transfer arm 5 and returned to the rack 3, and a new unobserved slide 2 is taken out from the rack 3.

  When the microscope apparatus 4 finishes obtaining the enlarged image, the control unit 6 determines whether or not the observation of all the slides 2 has been completed (step S18), and if not, activates the stage 8. Then, the slide 2 for which the enlarged image has been acquired (the observed slide 2) is moved to the take-out position for transfer by the transfer arm 5 (step S11), and the above steps are repeated. This take-out position is a position at which another empty slide holder portion 12c on which the slide 2 is not mounted is arranged on the optical axis C1 of the macro photographing optical system 9.

  At this time, the slide 2 from which the enlarged image has been acquired is arranged at a position deviated from the optical axis C1 of the macro photographing optical system 9. For example, as illustrated in FIG. 6B, the slide 2 (the observed slide 2) for which the enlarged image has been acquired is held by the slide holder unit 12 b and is at a position away from the lower position of the macro photographing optical system 9. Has been placed.

Accordingly, as shown in FIG. 6C, the transfer arm 5 that takes out a new unobserved slide 2 from the rack 3 and stands by in the vicinity of the macro photographing optical system 9 is light of the macro photographing optical system 9. The unobserved slide 2 is transferred to an empty slide holder portion 12c arranged on the axis C1, and the slide 2 from which the enlarged image has been acquired is acquired from the slide holder portion 12b during the acquisition of the entire image of the slide 2. It can be taken out.
That is, in this embodiment, the slide 2 before observation is always carried by the transfer arm 5 from a certain position to the slide holder portion 12b or 12c located on the optical axis C1 of the macro photographing optical system 9. Then, the observed slide 2 is carried out by the transfer arm 5 from the slide holder portion 12b or 12c which is off the optical axis C1 of the macro photographing optical system 9.

  As described above, according to the microscope system 1 according to the present embodiment, by providing the two slide holder portions 12b and 12c, the specimen A on the slide 2 arranged in one slide holder portion 12b (or 12c) is provided. During the acquisition of the entire image, the observed slide 2 arranged on the other slide holder portion 12c (or 12b) can be collected by the transfer arm 5. Accordingly, after the observed slide 2 arranged in the single slide holder portion 12 is collected by the transfer arm 5 and returned to the rack 3, the unobserved slide 2 is newly taken out from the rack 3 and transported. The time required for the work to be transferred to the slide holder unit 12 does not have to be stacked on all the slides 2, and when observing a large number of slides 2, the time can be significantly reduced.

Further, according to the microscope system 1 according to the present embodiment, the macro holder optical system includes the slide holder portion 12b (or 12c) on which the observed slide 2 is arranged after the enlarged image acquisition in the magnified optical system 10 is completed. Since the empty slide holder portion 12c (or 12b) is returned to the optical axis C1 of the macro photographing optical system 9 instead of returning to the ninth optical axis C1, the transfer arm 5, which has been waiting, is operated by the macro photographing optical. The unobserved slide 2 can be arranged on the optical axis C1 of the system 9, and the entire image can be acquired immediately after that to further reduce the required time.
In this embodiment, the two slide holder portions 12b and 12c are provided on the slide holder 12 mounted on the stage 8, but instead of this, three or more slide holder portions are provided. Also good.
Furthermore, in the present embodiment, the transfer arm 5 is one, but a plurality of transfer arms may be provided.

A Specimen 1 Microscope system 2 Slide 3 Rack (container)
4 Microscope device 5 Transfer arm 6 Control unit 7 Bar code (identification mark)
8 Stage 9 Macro shooting optical system 10 Enlarged shooting optical system 11 Bar code reader (sign reading device)
12 Slide holder

Claims (7)

A stage that mounts a slide with a specimen and moves it horizontally,
A microscope apparatus having a plurality of slide holder portions provided on the stage and capable of mounting a plurality of the slides in parallel;
An accommodating portion accommodating a plurality of the slides carrying the specimen;
At least one transfer arm for transferring the slide between the accommodating portion and the slide holder portion of the microscope apparatus;
The transfer arm transfers the unobserved slide from the storage unit to any empty slide holder unit, and transfers the other slide to the transfer arm during acquisition of the image of the specimen on the slide. And a control unit that controls the microscope apparatus and the transfer arm to be conveyed by the microscope system.   The microscope system according to claim 1, wherein the acquisition of the image of the specimen is photographing by the microscope device.   The control unit controls the microscope apparatus and the transfer arm so as to transfer another slide from another slide holder unit to the transfer arm during acquisition of an image of the specimen on the slide. The microscope system according to claim 1. A movable range of the slide by the stage is disposed so as to be able to face the slide, and includes an enlarged photographing optical system for magnifying and observing the specimen and a macro photographing optical system for obtaining an entire image of the specimen,
The microscope system according to claim 3, wherein acquisition of the image of the specimen is imaging by the macro imaging optical system.   The control unit is configured to place the slide, which has acquired the entire image of the specimen by the macro imaging optical system, facing the enlarged imaging optical system, and to mount the slide that has been enlarged and observed by the enlarged imaging optical system 5. The microscope system according to claim 4, wherein the stage is controlled such that a slide holder unit different from that of the macro photographing optical system is disposed opposite to the stage.   The control unit performs image processing on the entire image of the specimen acquired by the macro imaging optical system, specifies an observation area to be magnified, and controls the stage so as to magnify and photograph the identified observation area. The microscope system according to claim 4 or 5. Each slide is provided with a readable identification mark including identification information of the slide,
A sign reader for reading the identification sign;
A storage unit that associates and stores the identification mark and the observation condition of the specimen on the slide provided with the identification mark;
The microscope system according to claim 4 or 5, wherein the control unit reads the observation condition corresponding to the identification information included in the identification mark read by the sign reading device from the storage unit and controls the microscope device. .

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