Observation device

Abstract

To provide an observation device which is compact and can achieve the high throughput.SOLUTION: An observation device 1 comprises: a macro observation system which images a sample at the reduction magnification; and a micro observation system which contains a nosepiece to which a plurality of objective lenses can be attached and images the sample at the unity magnification or the enlargement magnification. The macro observation system and the micro observation system are arranged so as to satisfy a first condition. In the first condition, a distance c from a macro optical axis P1 to a micro optical axis P2 is equal to or less than the square sum root of the first distance a and the second distance b. The first distance a is the distance between the macro optical axis P1 and the outer diameter center axis P3 of the nosepiece. The second distance b is the distance in the first direction between the outer diameter center axis P3 and the side surface of the nosepiece. The first direction is the direction orthogonal to the macro optical axis P1 and orthogonal to a line segment connecting the macro optical axis P1 and the micro optical axis P2.SELECTED DRAWING: Figure 3

Description

Technical Field

[0001] The disclosure of this specification relates to an observation device.

Background Art

[0002] In a general observation device, it takes a lot of time to observe the entire container such as a well plate. This is because the field of view is too narrow for the entire container. In order to quickly observe the whole, a macro-observation system having a large-diameter lens that achieves both a wide field of view and telecentricity is effective. Such a technique is described in, for example, Patent Document 1. By using the macro-observation system, the efficiency of the observation work can be improved.

[0003] Further, Patent Document 2 describes a microscope provided with both a macro-observation system and a micro-observation system. By using a device having a macro-observation system and a micro-observation system, the efficiency of the observation work can be further improved.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0005] However, if a macro-observation system and a micro-observation system are simply provided side by side, the device will become large. This is because the micro-observation system usually includes a nosepiece for switching the objective lens, and it is necessary to arrange them at a distance so that the nosepiece and the macro-observation system do not interfere with each other inside the device.

[0006] Moreover, the greater the distance between the macro-observation system and the micro-observation system, the longer the moving distance of the stage when switching from macro-observation to micro-observation, and the longer the waiting time for the user. Therefore, if the macro-observation system and the micro-observation system are not appropriately arranged, the improvement in throughput obtained by co-locating the macro-observation system and the micro-observation system will fall short of the user's expectations.

[0007] Based on the above circumstances, an object according to one aspect of the present invention is to provide an observation apparatus capable of realizing a compact and high throughput.

Means for Solving the Problems

[0008] An observation apparatus according to one embodiment of the present invention includes a macro-observation system that photographs a specimen at a reduced magnification, and a micro-observation system that includes a nosepiece to which a plurality of objective lenses can be attached and photographs the specimen at an equal magnification or an enlarged magnification. The macro-observation system and the micro-observation system are arranged so as to satisfy a first condition. The first condition is that the distance from the macro-optical axis, which is the optical axis of the macro-observation system, to the micro-optical axis, which is the optical axis of the micro-observation system, is equal to or less than the square root of the sum of the squares of a first distance and a second distance. The second condition is that the magnitude of the acute angle formed by the first plane and the second plane is 40 degrees or less. The first distance is the distance between the macro-optical axis and the outer diameter central axis of the nosepiece. The second distance is the distance in a first direction between the outer diameter central axis and the side surface of the nosepiece. The first direction is a direction that is orthogonal to the macro-optical axis and orthogonal to the line segment connecting the macro-optical axis and the micro-optical axis. The first plane is a plane including the macro optical axis and the outer diameter central axis. The second plane is a plane parallel to the front surface of the observation device facing the user and parallel to the macro optical axis. The diagonal length of the shooting range of the macro observation system is 80 mm or more. The angle of the outermost chief ray on the object side of the macro observation system is within ±5 degrees. The depth of field of the macro observation system is ±2.5 mm or more.

Advantages of the Invention

[0009] According to the above aspect, it is possible to provide an observation apparatus capable of realizing a compact and high throughput.

Brief Description of the Drawings

[0010]

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Mode for Carrying Out the Invention

[0011] [First Embodiment] FIG. 1 is a perspective view of the observation device 1 according to the present embodiment. FIG. 2 is a top view of the observation device 1 according to the present embodiment. The observation device 1 is an observation device provided with both a macro-observation system 10 and a micro-observation system 20, and is used for both macro-observation and micro-observation. The observation device 1 further includes an epi-illumination system 30 used for micro-observation and a motorized stage 40 on which a specimen is placed.

[0012] As shown in FIG. 1, the observation device 1 is an inverted observation device in which both the macro-observation system 10 and the micro-observation system 20 are arranged below the motorized stage 40. Therefore, the observation device 1 can observe a specimen from the same direction in both macro-observation and micro-observation.

[0013] The macro-observation system 10 projects a specimen at a reduced magnification and captures an image using an image sensor (not shown). Although not shown, the observation device 1 may include a transmitted illumination system corresponding to the macro-observation system 10. The macro-observation system 10 may be used to observe a specimen illuminated from vertically above by the transmitted illumination system from vertically below.

[0014] The micro-observation system 20 projects a specimen at the same magnification or an enlarged magnification and captures an image using an image sensor (not shown). As shown in FIGS. 1 and 2, the micro-observation system 20 includes a nosepiece 21 to which a plurality of objective lenses can be attached. The nosepiece 21 is a revolving nosepiece. By rotating the nosepiece 21 around the rotation axis, the objective lens disposed on the optical axis of the micro-observation system 20 is switched.

[0015] As shown in FIGS. 1 and 2, the micro-observation system 20 has a configuration in which the optical path is bent halfway. Thereby, it is possible to avoid the position of the motorized stage 40 becoming too high with respect to the installation surface of the observation device 1. Therefore, the observation device 1 can provide the user with high workability with respect to the specimen on the motorized stage 40.

[0016] The epi-illumination system 30 illuminates a region that intersects the optical axis of the microscopic observation system 20. As shown in FIGS. 1 and 2, the epi-illumination system 30 extends in a direction orthogonal to the optical axis of the microscopic observation system 20. The illumination light emitted from the epi-illumination system 30 is deflected in the direction of the optical axis of the microscopic observation system 20 by a beam splitter (not shown) provided on the optical axis of the microscopic observation system 20, and is guided to a specimen placed on the motorized stage 40. Unless otherwise specified, the optical axis of the microscopic observation system 20 refers to the optical axis of the microscopic observation system 20 on the object side, which coincides with the optical axis of the objective lens used for microscopic observation. Also, unless otherwise specified, the optical axis of the epi-illumination system 30 refers to the optical axis of the epi-illumination system 30 on the object side, which coincides with the optical axis of the objective lens used for microscopic observation. That is, the direction of the optical axis of the epi-illumination system 30 refers to the direction of the optical axis of the objective lens. On the other hand, the direction of the optical axis of the epi-illumination system 30 before being deflected in the direction coinciding with the optical axis of the objective lens by the beam splitter is referred to as the extending direction of the epi-illumination system 30, which is distinguished from the above-described direction of the optical axis of the epi-illumination system 30.

[0017] The motorized stage 40 is a moving stage that moves the specimen. More specifically, the motorized stage 40 is an XY stage that moves in a direction orthogonal to the optical axis of the macroscopic observation system 10 and the optical axis of the microscopic observation system 20. By moving the motorized stage 40, it is possible to move the specimen placed on the motorized stage 40 back and forth between the optical axis of the macroscopic observation system 10 and the optical axis of the microscopic observation system 20, and it is possible to smoothly switch between macroscopic observation and microscopic observation.

[0018] FIG. 3 is a diagram for explaining an example of a desirable arrangement relationship between the macroscopic observation system and the microscopic observation system according to the present embodiment. FIG. 4 is a diagram for explaining an example of an undesirable arrangement relationship between the macroscopic observation system and the microscopic observation system. FIG. 5 is a diagram showing the movable range of the motorized stage in the arrangement relationship shown in FIG. 3. FIG. 6 is a diagram showing the movable range of the motorized stage in the arrangement relationship shown in FIG. 4.

[0019] Hereinafter, with reference to FIGS. 3 to 6, the desirable arrangement relationship between the macro observation system 10 and the micro observation system 20 will be described by paying attention to the distance between the optical axis of the macro observation system 10 and the optical axis of the micro observation system 20. Hereinafter, the optical axis of the macro observation system 10 will be denoted as the macro optical axis P1, and the optical axis of the micro observation system 20 will be denoted as the micro optical axis P2.

[0020] In order to configure the observation apparatus 1 to be compact and achieve high throughput, it is desirable to arrange the macro observation system 10 and the micro observation system 20 as close to each other as possible. On the other hand, if the macro observation system 10 and the micro observation system 20 are too close to each other, for example, when the nosepiece 21 is rotated, the objective lens may come into contact with the macro observation system 10, and the macro observation system 10 and the micro observation system 20 may interfere with each other. Further, even if the macro observation system 10 and the micro observation system 20 do not directly interfere with each other, the epi-illumination system 30 used for micro observation may interfere with the macro observation system 10.

[0021] As a result of intensive studies by the inventors in consideration of the above points, it has been found that it is desirable that the macro observation system 10 and the micro observation system 20 be arranged so as to satisfy the following conditions (hereinafter referred to as the first condition) as shown in FIG. 3. In FIG. 3, the side surface of the nosepiece 21 is represented by the outer contour line L21.

[0022] First condition: The optical axis distance c from the macro optical axis P1 to the micro optical axis P2 is the square root of the sum of the squares of the first distance a and the second distance b ((a 2 +b 2 ) 1 / 2 ) or less. First distance a: The distance between the macro optical axis P1 and the outer diameter central axis P3 of the nosepiece 21 Second distance b: The distance in the first direction between the outer diameter central axis P3 and the side surface of the nosepiece 21 First direction: A direction perpendicular to the macro optical axis P1 and perpendicular to the line segment connecting the macro optical axis P1 and the outer diameter central axis P3

[0023] That is, in the observation apparatus 1, for the macro observation system 10 and the micro observation system 20, c ≦ (a 2 +b 2) 1 / 2 It is desirable to be arranged so as to satisfy this. This first condition defines where the objective lens of the microscopic observation system 20 should be arranged when the nose piece 21 is rotated and the nose piece 21 is arranged at a distance from the macroscopic observation system 10 so that the objective lens of the microscopic observation system 20 does not contact the macroscopic observation system 10. Specifically, when the distance c between the optical axes is a predetermined distance (a 2 +b 2 ) 1 / 2 It is defined that the microscopic optical axis P2 should be arranged as follows. The shaded area in FIG. 4 indicates the area where the microscopic optical axis P2 can be arranged when the first condition is satisfied.

[0024] When the arrangement of the macroscopic observation system 10 and the nose piece 21 (macroscopic optical axis P1 and outer diameter central axis P3) is determined as shown in FIGS. 3 and 4 so that the objective lens of the microscopic observation system 20 does not contact the macroscopic observation system 10, the arrangement of the microscopic optical axis P2 is limited to the area within the outer contour line L21 of the nose piece 21. At this time, for example, as shown in FIG. 4, if the microscopic optical axis P2 is placed at a position relatively far from the macroscopic optical axis P1 in the area within the outer contour line L21, the moving amount of the electric stage 40 will increase when switching from macroscopic observation to microscopic observation. Therefore, it becomes difficult to achieve high throughput. On the contrary, as shown in FIG. 3, by placing the microscopic optical axis P2 at a position relatively close to the macroscopic optical axis P1 in the area within the outer contour line L21, the moving amount of the electric stage 40 can be reduced when switching from macroscopic observation to microscopic observation, and high throughput can be achieved.

[0025] Also, as shown in FIGS. 5 and 6, by satisfying the first condition, any position of the container 2 can be observed with a small footprint L40 of the electric stage 40. Specifically, the footprint L40 when the first condition shown in FIG. 5 is satisfied is smaller than the footprint L40 when the first condition shown in FIG. 6 is not satisfied. Therefore, it is possible to avoid a situation where the movable range of the electric stage 40 becomes a constraint condition for making the observation apparatus 1 compact.

[0026] Note that in the first condition, by setting the distance c between the optical axes to be less than or equal to the square root of the sum of the squares of the first distance a and the second distance b, compared to the case where the distance c between the optical axes is, for example, less than or equal to the first distance a, some degree of freedom is given to the region where the micro optical axis P2 is arranged. This is because, for example, when the micro optical axis P2 is placed between the macro optical axis P1 and the outer diameter central axis P3, while the movement amount of the stage can be suppressed to be short, it is necessary to insert one end of the epi-illumination system 30 into the macro optical axis P1 and the outer diameter central axis P3. Considering that it is difficult to arrange the epi-illumination system 30 without contacting the macro observation system 10. By setting the distance c between the optical axes to be less than or equal to the square root of the sum of the squares of the first distance a and the second distance b, it becomes easier to arrange the macro observation system 10 and the micro observation system 20 so that the epi-illumination system 30 does not interfere with the macro observation system 10. Therefore, the observation device 1 can be configured compactly without separating the macro observation system 10 and the micro observation system 20 more than necessary for arranging the epi-illumination system 30.

[0027] FIG. 7 is a diagram for explaining another example of a desirable arrangement relationship between the macro observation system and the micro observation system according to the present embodiment. FIG. 8 is a top view of the observation device 1 in the arrangement relationship shown in FIG. 7. Hereinafter, with reference to FIGS. 7 and 8, the desirable arrangement relationship between the macro observation system 10 and the micro observation system 20 will be described while focusing on the direction in which the macro observation system 10 and the micro observation system 20 are aligned.

[0028] When the surface facing the user is defined as the front surface of the observation device 1, in order to facilitate access to the specimen in both macro observation and micro observation, it is desirable that the macro observation system 10 and the micro observation system 20 are aligned in the width direction (x direction) parallel to the front surface and orthogonal to the macro optical axis P1 rather than in the depth direction (y direction) orthogonal to the front surface and orthogonal to the macro optical axis P1.

[0029] Specifically, as shown in FIG. 7, it is desirable that the macro observation system 10 and the micro observation system 20 be arranged to satisfy the following conditions (hereinafter referred to as the second condition). In FIG. 7, the first plane is represented by a straight line connecting the macro optical axis P1 and the outer diameter center axis P3. The second plane is represented by a straight line LX passing through the outer diameter center axis P3.

[0030] Second condition: The magnitude of the acute angle θ formed by the first plane and the second plane is 40 degrees or less. First plane: A plane including the macro optical axis P1 and the outer diameter center axis P3 Second plane: A plane parallel to the front surface of the observation device and parallel to the macro optical axis P1

[0031] In a configuration that satisfies the second condition, as shown in FIG. 8, neither the macro optical axis P1 (the center of the macro observation system 10) nor the micro optical axis P2 is very far from the user sitting near the front surface F. Therefore, whether a specimen is placed on the macro optical axis P1 or on the micro optical axis P2, the user can easily access the specimen from the front surface F side, which contributes to an improvement in throughput.

[0032] As shown in FIG. 8, there being few obstacles between the front surface F and the optical axis also contributes to achieving high accessibility. In this configuration, for example, access to components other than the specimen that the user directly operates, such as the objective lens and the fluorescence filter cube, also becomes easier. Furthermore, by arranging the macro optical axis P1 and the micro optical axis P2 in the width direction (x direction), the shape of the entire observation device 1 is likely to be a horizontally long shape that is long in the width direction (x direction). The shape of the tabletop of the experimental machine on which the observation device 1 is installed is usually also horizontally long. Therefore, this configuration is also desirable in that it can effectively utilize the tabletop.

[0033] FIG. 9 is a diagram for explaining still another example of a desirable arrangement relationship between the macroscopic observation system and the microscopic observation system according to the present embodiment. FIG. 10 is a top view of the observation apparatus 1 in the arrangement relationship shown in FIG. 9. Hereinafter, with reference to FIGS. 9 and 10, the desirable arrangement relationship between the macroscopic observation system 10 and the microscopic observation system 20 will be described while paying attention to the positional relationship among the macroscopic optical axis P1, the microscopic optical axis P2, and the outer diameter center axis P3.

[0034] When the epi-illumination system 30 is adopted for the illumination system, in addition to the macroscopic observation system 10 and the microscopic observation system 20, the epi-illumination system 30 is disposed below the electric stage 40. Therefore, in order to configure the observation apparatus 1 compactly, it is essential to efficiently utilize the space below the electric stage 40 to arrange the macroscopic observation system 10, the microscopic observation system 20, and the epi-illumination system 30.

[0035] Although the epi-illumination system 30 extends in a direction parallel to the electric stage 40 (a direction parallel to the xy plane), one end of the epi-illumination system 30 reaches onto the microscopic optical axis P2. Considering this point, in order to avoid the epi-illumination system 30 from interfering with the macroscopic observation system 10 or the nose piece 21, it is desirable to arrange the microscopic optical axis P2 at a position deviated from the plane connecting the macroscopic optical axis P1 and the outer diameter center axis P3.

[0036] Specifically, as shown in FIG. 9, it is desirable that the macroscopic observation system 10 and the microscopic observation system 20 be arranged so as to satisfy the following condition (hereinafter referred to as the third condition). In FIG. 9, the regions satisfying the first condition and the third condition are shown hatched. Also, the first cylinder is represented by the outer contour line L10, and the two tangent planes are represented by the tangent line LT1 and the tangent line LT2.

[0037] Third condition: The microscopic optical axis P2 is arranged within the first region First region: A region corresponding to the obtuse angle formed by the two tangent planes among the two regions partitioned by the two tangent planes drawn from the outer diameter center axis P3 toward the side surface of the first cylinder First cylinder: A cylinder having the maximum outer diameter of the macroscopic observation system 10 as the diameter and the macroscopic optical axis P1 as the cylinder axis

[0038] In the configuration that satisfies the third condition, as shown in FIG. 10, it is possible to avoid inserting the epi-illumination system 30 into the narrow space between the macro-observation system 10 and the nosepiece 21. Therefore, in order to arrange the epi-illumination system 30, it is not necessary to overly separate the macro-observation system 10 and the micro-observation system 20, and the observation device 1 can be configured to be compact.

[0039] FIG. 11 is a diagram for explaining an example of a desirable arrangement of the epi-illumination system according to the present embodiment. FIG. 12 is a top view of the observation device 1 in the arrangement shown in FIG. 11. Hereinafter, with reference to FIGS. 11 and 12, the desirable arrangement of the epi-illumination system 30 will be described while paying attention to the relationship with components other than the epi-illumination system 30.

[0040] The epi-illumination system 30 extends in a direction parallel to the electric stage 40 (a direction parallel to the xy plane). Therefore, depending on the direction in which the epi-illumination system 30 is arranged, the footprint of the observation device 1 may become large. The epi-illumination system 30 is desirably arranged in an appropriate direction so that the footprint of the observation device 1 when the epi-illumination system 30 is arranged does not become overly large compared to the footprint of the observation device 1 when the epi-illumination system 30 is not arranged.

[0041] Specifically, as shown in FIG. 11, the epi-illumination system 30 is desirably arranged so as to satisfy the following conditions (hereinafter referred to as the fourth condition). The projection plane is, for example, the xy plane on which the electric stage 40 moves. In FIG. 11, the overlapping region between the first region and the third region is shown hatched. Also, the movable range of the electric stage 40 is represented by the footprint L40 of the electric stage 40, and the minimum rectangular region described later is represented by the outer contour line LP. Also, the short side direction of the movable range is the depth direction (y direction) of the observation device 1.

[0042] Fourth condition: The angle formed between the extending direction of the epi-illumination system 30 and the second plane is within the central angle range of the arcs (arc A1, arc A2) formed by projecting the overlapping region between the first region and the third region onto the projection plane orthogonal to the optical axis P1 of the macro-observation system 10. However, the central angle range is the range of the angle represented by the angle formed by the arc and the second plane. Second region: The smallest rectangular region that includes the entire movable ranges of the macro-observation system 10, the micro-observation system 20, and the electric stage 40 Third region: The region occupied by a cylinder with the outer diameter central axis P3 as the cylinder axis and with a radius equal to the maximum distance in the short side direction (y direction) of the movable range of the electric stage 40 between the outer diameter central axis P3 and the outer contour line LP that demarcates the second region

[0043] In a configuration that satisfies the fourth condition, as shown in FIG. 12, the epi-illumination system 30 can be arranged without increasing the footprint of the observation apparatus 1. Therefore, the observation apparatus 1 can be configured to be compact.

[0044] FIG. 13 is a diagram for explaining another example of a desirable arrangement of the epi-illumination system according to the first embodiment. Above, the case where the micro-observation system 20 has a configuration in which the optical path is bent midway has been described as an example, but the micro-observation system 20 does not necessarily have to have a configuration in which the optical path is bent midway. FIG. 13 shows a desirable arrangement of the epi-illumination system when the micro-observation system 20 does not have a configuration in which the optical path is bent midway.

[0045] As shown in FIG. 13, when the micro-observation system 20 does not have a configuration in which the optical path is bent, inevitably the footprint of the observation apparatus 1 also becomes smaller. For this reason, the region where the epi-illumination system 30 can be arranged without increasing the footprint also becomes smaller. For this reason, the constraints on the size of the epi-illumination system 30 become stricter. On the other hand, if the constraints on the size can be satisfied, as represented by the shaded region in FIG. 13, the constraints on the orientation of the epi-illumination system 30 become looser, and the epi-illumination system 30 can be oriented in a relatively free direction.

[0046] FIG. 14 is a diagram for explaining desirable characteristics of the macro observation system. FIG. 15 is a graph showing the relationship between the number of wells and the ratio of the observable area of the well bottom surface. FIG. 16 is a table showing the relationship between the numerical aperture, the depth of field, and the cut-off frequency. FIG. 17 is a graph showing the relationship between the frequency and the MTF. Hereinafter, with reference to FIGS. 14 to 17, the desirable characteristics of the macro observation system 10 will be described.

[0047] The macro observation system 10 desirably has a wide field of view. Specifically, for example, assuming a well plate as the container 2, the diagonal length of the imaging range of the macro observation system 10 is desirably 80 mm or more. The size of a general well plate is determined to be 128 mm × 85 mm. When the well plate is divided into upper and lower parts, the diagonal length of the divided range is approximately 77 mm. Therefore, by having an imaging range with a diagonal length of 80 mm, the observation device 1 can construct an image of the entire well plate by taking two images of the well plate separately and synthesizing the two images.

[0048] The macro observation system 10 desirably has high telecentricity. Specifically, for example, assuming a well plate having many wells such as 96 wells as the container 2, the principal ray angle of the outermost object side of the macro observation system 10 is desirably within ±5 degrees. Thereby, since the state inside each well can be correctly grasped by macro observation, the well to be observed by micro observation can be appropriately specified.

[0049] Note that the graph shown in Fig. 15 shows the results of calculating the observable well bottom area (hereinafter referred to as the aperture ratio) with respect to the actual well bottom area based on the information on the well height h and the radius r of the well bottom (see Fig. 14) for each of the well plates of 6 wells, 12 wells, 24 wells, 48 wells, and 96 wells. As the number of wells increases and as the magnitude of the principal ray angle φ increases, the image of the well side is significantly reflected on the well bottom, so the aperture ratio tends to decrease as shown in Fig. 15. However, by suppressing the magnitude of the principal ray angle within 5 degrees, even when using a well plate with 96 wells, which has the most stringent conditions, more than 80% of the area of the well can be observed normally.

[0050] The macro observation system 10 generally does not have an autofocus function. Therefore, it is desirable to have a deep depth of field. Specifically, the depth of field is desirably ±2.5 mm or more. This is because the height of the well bottom of the well plate varies depending on the well plate manufacturer, the shape of the well, etc., but generally falls within the range of about 0.4 mm to 4.8 mm. Therefore, with a depth of field of 5 mm in total width, it is possible to focus on the bottom of the well regardless of the well plate even without an autofocus function.

[0051] The macro observation system 10 desirably has the characteristic of being able to distinguish the wells of the well plate with good contrast. The table shown in Fig. 16 shows the relationship between the numerical aperture, the depth of field, and the cut-off frequency. The higher the numerical aperture of the optical system, the higher the contrast and the higher the cut-off frequency, but as shown in Fig. 16, on the other hand, the depth of field becomes narrower. Therefore, the numerical aperture of the macro observation system 10 is desirably designed to have sufficient contrast and sufficient depth of field according to the use of the macro observation system 10.

[0052] The side surface of each well is about 1 mm. Therefore, in order to clearly distinguish the wells, it is desirable that the macro observation system 10 has a high contrast with respect to a spatial frequency of 1 line / mm on the object plane. As shown in FIG. 17, at a frequency obtained by multiplying the cut-off frequency of the optical system by 0.15, the MTF shows 80% or more of the maximum contrast. That is, since a sufficiently high contrast can be obtained at a frequency that is 0.15 times the cut-off frequency, any optical system in which the frequency that is 0.15 times the cut-off frequency is 1 mm or more can satisfy the requirement of clearly distinguishing the wells. Further, considering the condition (±2.5 or more) required for the depth of field described above, the desirable range of the numerical aperture of the macro observation system 10 is, for example, 0.002 or more and 0.01 or less, as shown in FIG. 16. That is, the macro observation system 10 for the well plate can observe any well plate with high contrast and with the bottom surface of the well in focus by having a numerical aperture in the range of 0.002 to 0.01.

[0053] FIG. 18 is a diagram showing an example of the lens configuration of the macro observation system. FIG. 19 is a diagram showing another example of the lens configuration of the macro observation system. FIG. 20 is a diagram showing still another example of the lens configuration of the macro observation system. With reference to FIGS. 18 to 20, an example of the lens configuration of the macro observation system will be described.

[0054] As shown in FIG. 18, the macro observation system 10 includes a single large-aperture lens (lens L1). Further, it includes a plurality of lenses near the aperture stop. Note that the large-aperture lens is not limited to one, and a plurality of lenses may be provided. The macro observation system 11 shown in FIG. 19 has a configuration including two large-aperture lenses (lens L1 and lens L2). Also, the large-aperture lens may be composed of a Fresnel lens. The macro observation system 12 shown in FIG. 20 has a configuration including a large-aperture lens (lens LF) composed of a Fresnel lens. The observation device 1 may adopt any of the optical systems from the macro observation system 10 shown in FIG. 18 to the macro observation system 12 shown in FIG. 20.

[0055] [Second Embodiment] The observation apparatus according to this embodiment (hereinafter simply referred to as "this observation apparatus") is different from the observation apparatus 1 according to the first embodiment in that a slide-type nosepiece is adopted for the nosepiece of the microscopic observation system 20. The slide-type nosepiece is similar to the revolving nosepiece in that it is a nosepiece on which a plurality of objective lenses can be mounted, but is different from the revolving nosepiece in that the objective lens arranged on the optical axis of the microscopic observation system 20 is switched by translating a plurality of objective lenses in parallel. Other points are the same as those in the first embodiment. Among the configurations included in this observation apparatus, the same configurations as those of the observation apparatus 1 are referred to using the same reference numerals as those of the observation apparatus 1.

[0056] Hereinafter, in order to achieve compactness and high throughput, the desirable conditions satisfied by this observation apparatus provided with a slide-type nosepiece will be described.

[0057] FIG. 21 is a diagram for explaining an example of a desirable arrangement relationship between the macro observation system and the micro observation system according to this embodiment, and is an example in which the slide-type nosepiece is in the reference position. FIG. 22 is a diagram for explaining an example of a desirable arrangement relationship between the macro observation system and the micro observation system according to this embodiment, and is an example in which the slide-type nosepiece has slid from the reference position. FIG. 23 is a diagram for explaining an example of an undesirable arrangement relationship between the macro observation system and the micro observation system, and is an example in which the slide-type nosepiece is in the reference position. FIG. 24 is a diagram for explaining an example of an undesirable arrangement relationship between the macro observation system and the micro observation system, and is an example in which the slide-type nosepiece has slid from the reference position.

[0058] Also in this observation apparatus, similar to the observation apparatus 1 according to the first embodiment, it is desirable that the macro observation system 10 and the micro observation system 20 are arranged so as to satisfy the first condition described above in the first embodiment. That is, the macro observation system 10 and the micro observation system 20 satisfy c ≦ (a 2 + b 2 ) 1 / 2It is desirable to be arranged so as to satisfy the condition. In FIGS. 21 and 22, the contour of the nose piece 22 is represented by the outer contour line L22.

[0059] Also in this observation device, similar to the observation device 1, the distance c between the macro optical axis P1 and the micro optical axis P2 is constant. However, since the outer diameter central axis P3 changes when the nose piece 22 slides, in this observation device, the distances a and b change depending on the state of the nose piece 22. It is desirable that the macro observation system 10 and the micro observation system 20 in this observation device be arranged so as to satisfy the first condition regardless of the state of the nose piece 22 as shown in FIGS. 21 and 22. Thereby, since an arrangement in which the macro optical axis P1 and the micro optical axis P2 are too far apart can be avoided, the device can be configured compactly.

[0060] Note that in the observation device shown in FIGS. 21 and 22, the nose piece 22 moves in a direction orthogonal to the line segment connecting the macro optical axis P1 and the micro optical axis P2. On the other hand, in the examples shown in FIGS. 23 and 24 in which the macro observation system 10 and the micro observation system 20 are arranged so as not to satisfy the first condition, the direction in which the nose piece 22 slides is different from the direction orthogonal to the line segment connecting the macro optical axis P1 and the micro optical axis P2. Such an arrangement causes the nose piece 22 to move to a position far from the macro observation system 10 depending on the state of the nose piece 22. For this reason, it becomes difficult to configure the device compactly.

[0061] FIG. 25 is a diagram for explaining another example of a desirable arrangement relationship between the macro observation system and the micro observation system, and is an example in which the slide-type nose piece is in the reference position. FIG. 26 is a diagram for explaining still another example of a desirable arrangement relationship between the macro observation system and the micro observation system, and is an example in which the slide-type nose piece has slid from the reference position.

[0062] The macro observation system 10 and the micro observation system 20 are preferably arranged so as to satisfy the second condition described above. In this observation apparatus, since the outer diameter central axis P3 changes when the nosepiece 22 slides, the angle θ changes depending on the state of the nosepiece 22. As shown in FIGS. 25 and 26, by setting the slide direction to the depth direction and arranging it so that θ at the reference position becomes sufficiently small, the second condition can be satisfied. By arranging it so as to satisfy the second condition, the macro observation system 10 and the micro observation system 20 will be arranged side by side in the width direction (x direction) of the apparatus. Therefore, it is possible to provide a user with an apparatus in which the entire apparatus is configured in a horizontally long shape, is easily accessible to the specimen, and realizes high throughput.

[0063] FIG. 27 is a diagram for explaining still another example of a desirable arrangement relationship between the macro observation system and the micro observation system according to the present embodiment.

[0064] The macro observation system 10 and the micro observation system 20 are preferably arranged so as to satisfy the third condition described above as shown in FIG. 27. By arranging it so as to satisfy the third condition, it is possible to avoid the epi-illumination system 30 being inserted into the narrow space between the macro observation system 10 and the nosepiece 21, and as a result, the observation apparatus can be configured compactly. In FIG. 27, the regions satisfying the first condition and the third condition are shown hatched.

[0065] The above-described embodiments are presented with specific examples to facilitate the understanding of the invention, and the present invention is not limited to these embodiments. Modified forms of the above-described embodiments and alternative forms that replace the above-described embodiments may be included. That is, each embodiment can have its components modified without departing from the spirit and scope thereof. Also, by appropriately combining a plurality of components disclosed in one or more embodiments, new embodiments can be implemented. Further, some components may be deleted from the components shown in each embodiment, or some components may be added to the components shown in the embodiment. Additionally, the processing procedures shown in each embodiment may be performed with the order changed as long as there is no contradiction. That is, the observation apparatus of the present invention can be variously modified and changed without departing from the description in the claims.

Explanation of Reference Numerals

[0066] 1 Observation apparatus 2 Container 10, 11, 12 Macro observation system 20 Micro observation system 21, 22 Nosepiece 30 Episcopic illumination system 40 Motorized stage P1 Macro optical axis P2 Micro optical axis P3 Outer diameter central axis L10, L21, L22, LP Outer contour line L40 Footprint LX Straight line LT1, LT2 Tangent line

Claims

1. An observation device, a macro-observation system for photographing a specimen at a reduced magnification, including a nosepiece to which a plurality of objective lenses can be attached, and a micro-observation system for photographing the specimen at a same magnification or an enlarged magnification, wherein the macro-observation system and the micro-observation system are arranged so as to satisfy a first condition and a second condition, the first condition is that a distance from a macro optical axis, which is an optical axis of the macro-observation system, to a micro optical axis, which is an optical axis of the micro-observation system, is equal to or less than a square root of a sum of squares of a first distance and a second distance, the second condition is that a magnitude of an acute angle formed by a first plane and a second plane is equal to or less than 40 degrees, the first distance is a distance between the macro optical axis and an outer diameter central axis of the nosepiece, the second distance is a distance in a first direction between the outer diameter central axis and a side surface of the nosepiece, the first direction is a direction orthogonal to the macro optical axis and orthogonal to a line segment connecting the macro optical axis and the micro optical axis, the first plane is a plane including the macro optical axis and the outer diameter central axis, the second plane is a plane parallel to a front surface of the observation device facing a user and parallel to the macro optical axis, a diagonal length of a photographing range of the macro-observation system is 80 mm or more, an off-axis principal ray angle of an object side of the macro-observation system is within ±5 degrees, a depth of field of the macro-observation system is ±2.5 mm or more The observation device is characterized by the above.

2. In the observation device according to claim 1, the macro-observation system and the micro-observation system are arranged so as to satisfy a third condition, the third condition is that the micro optical axis is arranged within a first region, The first region is a region corresponding to an obtuse angle formed by two tangent planes drawn from the center axis of the outer diameter of the nose piece toward the side surface of the first cylinder among two regions partitioned by the two tangent planes, The first cylinder is a cylinder having the maximum outer diameter of the macro observation system as its diameter and the macro optical axis as its cylinder axis. An observation apparatus characterized by the above.

3. In the observation apparatus according to claim 2, further, A moving stage for moving the specimen, An epi-illumination system for illuminating a region intersecting the micro optical axis, and The epi-illumination system is arranged to satisfy a fourth condition, The fourth condition is that the angle formed by the extending direction of the epi-illumination system and the second plane is within a central angle range of an arc formed by projecting an overlapping region between the first region and the third region onto a projection plane orthogonal to the optical axis of the macro observation system, and is within the central angle range represented by the angle formed with the second plane. The second region is a minimum rectangular region including all of the macro observation system, the micro observation system, and the movable range of the moving stage. The third region is a region occupied by a cylinder having the maximum distance in the short side direction of the movable range between the outer diameter central axis and an outer contour line partitioning the second region as its radius and the outer diameter central axis as its cylinder axis. An observation apparatus characterized by the above.

4. In the observation apparatus according to any one of claims 1 to 3, The nose piece is a revolving nose piece. An observation apparatus characterized by the above.

5. In the observation apparatus according to claim 1, further, A moving stage for moving the specimen, The macro observation system is arranged on one side, above or below, of the moving stage. The microscopic observation system is disposed on one side of the moving stage where the macroscopic observation system is disposed. An observation apparatus characterized by the above.

6. In the observation apparatus according to claim 3, the macroscopic observation system is disposed on one side above or below the moving stage, the microscopic observation system is disposed on one side of the moving stage where the macroscopic observation system is disposed, the epi-illumination system is disposed on one side of the moving stage where the macroscopic observation system is disposed An observation apparatus characterized by the above.

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