microscope
The microscope system addresses focus shifts and misalignments by using a shared objective lens and magnification adjustment device, allowing for rapid and efficient switching between observation methods and magnifications in ICSI.
Patent Information
- Application Number
- JP2021002410
- Authority / Receiving Office
- JP · JP
- Patent Type
- Patents
- Current Assignee / Owner
- Filing Date
- 2021-01-08
- Publication Date
- 2025-10-16
- Estimated Expiration
- 2041-01-08
AI Technical Summary
Existing microscopes used in intracytoplasmic sperm injection (ICSI) face issues with focus shifts and misalignment when switching between observation methods and magnifications, leading to inefficiencies and increased operation time.
A microscope system with a shared objective lens and a magnification adjustment device that allows for seamless switching between observation methods without changing the objective lens, using a magnification adjustment means to adjust optical magnification accordingly.
Enables quick and efficient switching between observation methods and magnifications, reducing adjustment time and ensuring smooth continuation of the observation process.
Smart Images

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Abstract
Description
[Technical Field]
[0001] The present disclosure relates to microscopes. [Background technology]
[0002] As people are getting married and having children later in life, the number of patients undergoing infertility treatment is increasing year by year, and the demand for assisted reproductive technology (ART) is also on the rise.
[0003] ART is a general term for techniques that involve fertilizing eggs and sperm extracted from a human outside the body, such as intracytoplasmic sperm injection (ICSI) and in vitro fertilization (IVF). It is distinct from conventional artificial insemination, in which collected sperm are injected into the uterus and fertilized with an egg inside the body.
[0004] Technologies related to ART are described, for example, in Patent Document 1. Patent Document 1 describes a microscope suitable for intracytoplasmic sperm injection (ICSI), which is used in intracytoplasmic sperm injection (ICS), a type of ART. ICSI is a method of directly injecting sperm into an egg by piercing an injection pipette containing sperm into the egg fixed with a holding pipette. [Prior art documents] [Patent documents]
[0005] [Patent Document 1] International Publication No. 2012 / 150689 Summary of the Invention [Problem to be solved by the invention]
[0006] In ICSI, embryologists select sperm under a microscope and inject those suitable for fertilization into eggs. To increase the success rate of ICSI, it is necessary to efficiently perform a series of tasks under the microscope in a short amount of time while switching between various observation methods and magnifications. By using the microscope described in Patent Document 1, embryologists can change the observation method and magnification at the touch of a button, simplifying microscope operation and thereby reducing work time.
[0007] However, in the microscope described in Patent Document 1, when changing the observation magnification along with the observation method, the objective lens is switched in response to a button operation. This can lead to a shift in focus due to slight differences in the parfocal distance between the objective lenses before and after switching. Furthermore, the center of the field of view can shift due to misalignment. When such an event occurs, the embryologist must spend time correcting these misalignments, preventing smooth continuation of observation after switching the observation method.
[0008] In view of the above circumstances, an object of one aspect of the present invention is to provide a technique that enables observation to be started quickly after switching the observation method and observation magnification. [Means for solving the problem]
[0009] A microscope apparatus according to one aspect of the present invention is a microscope used with a plurality of observation methods, the microscope apparatus comprising: an objective lens that is commonly used with the plurality of observation methods; and a microscope lens that is disposed on the image side of the objective lens and is used for switching between the plurality of observation methods. Together and a magnification adjustment means for adjusting the optical magnification of the microscope without switching the objective lens, wherein the magnification adjustment means has an optical system with a magnification according to the magnification ratio between the magnification of the objective lens and a predetermined magnification for the observation method, and when the optical magnification of the microscope is different from the predetermined magnification for the observation method after switching, the magnification of the optical system is adjusted to change the optical magnification of the microscope to the predetermined magnification. [Effects of the Invention]
[0010] According to the above aspect, it is possible to provide a technique that enables observation to be started quickly after switching the observation method and observation magnification. [Brief explanation of the drawings]
[0011] [Figure 1] 1 is a diagram illustrating an example of the configuration of a microscope system 1. FIG. [Figure 2] 1 is a diagram illustrating the configuration of a microscope 10. FIG. [Figure 3] 2 is a diagram illustrating an example of the configuration of an operation unit of the input device 3. FIG. [Figure 4] 10 is a diagram illustrating the relationship between a predetermined magnification for each observation method, the magnification of an objective lens, and the magnification of a magnification adjustment device. [Figure 5] 1 is a flowchart showing an example of a procedure for intracytoplasmic sperm injection. [Figure 6] 1 is a diagram illustrating the configuration of a microscope 100. FIG. [Figure 7] FIG. 2 is a diagram illustrating the configuration of a microscope 200. [Figure 8] FIG. 2 is a diagram illustrating the configuration of a microscope 300. [Figure 9] FIG. 4 is a diagram illustrating the configuration of a microscope 400. [Figure 10] FIG. 1 is a diagram illustrating the configuration of a microscope 500. [Figure 11] 1 is a diagram illustrating the configuration of a universal capacitor 600. FIG. [Figure 12] FIG. 7 is a diagram illustrating the configuration of a magnification adjustment device 700. [Figure 13] FIG. 1 is a diagram illustrating an example of the configuration of a microscope system 1a. DETAILED DESCRIPTION OF THE INVENTION
[0012] [First embodiment] Fig. 1 is a diagram illustrating the configuration of a microscope system 1. Fig. 2 is a diagram illustrating the configuration of a microscope 10. Fig. 3 is a diagram illustrating the configuration of an operation unit of an input device 3. Fig. 4 is a diagram illustrating the relationship between the predetermined magnification for each observation method, the magnification of the objective lens, and the magnification of the magnification adjustment device (intermediate magnification).
[0013] The microscope system 1 shown in Fig. 1 is a microscope system used for ICSI and the like, and includes a microscope 10 used for multiple observation methods. The user of the microscope system 1 is not particularly limited, but may be, for example, an embryologist. The sample observed by the microscope system 1 is, for example, a reproductive cell such as a sperm or egg contained in a petri dish, and is a phase object.
[0014] The microscope 10 includes at least an objective lens 40 that is commonly used for a plurality of observation methods, and a magnification adjustment device 70, which is an example of a magnification adjustment means that adjusts the optical magnification of the microscope 10 in response to switching between the plurality of observation methods. As shown in Fig. 1, the magnification adjustment device 70 is a device different from the revolver 45 that switches between the objective lenses 40, and is disposed on the image side of the objective lens 40. In this specification, "adjust" means that the object to be adjusted is changed if necessary, or not changed if not necessary.
[0015] Here, "microscopy" refers to a microscope observation method, also known as microscopy. Typical observation methods include bright field (BF) observation, dark field (DF) observation, polarized light (PO) observation, phase contrast (PC) observation, differential interference contrast (DIC) observation, fluorescence (FL) observation, and relief contrast (RC) observation. Note that relief contrast (RC) observation is also called modulation contrast (MC) observation.
[0016] The optical magnification of the microscope 10 refers to the magnification of the optical image of the sample formed by the microscope 10, and indicates how many times larger the optical image is than the sample. The optical magnification of the microscope 10 may be, for example, the observation magnification (total magnification) of the eyepiece tube 80 of the microscope 10, or the magnification on the imaging plane of the imaging device 90 of the microscope 10. The observation magnification (total magnification) on the monitor of the computer 4 included in the microscope system 1 is the magnification on the imaging plane multiplied by the monitor magnification. Therefore, in the microscope system 1, when the magnification adjustment device 70 adjusts the optical magnification of the microscope 10, the observation magnification is also adjusted at the same time.
[0017] In ICSI, as described below, the observation target or purpose differs for each observation method. Therefore, embryologists generally need to change the observation magnification when switching between observation methods. The observation magnification used for each observation method is roughly determined because it is limited by the observation target and purpose of that observation method. Therefore, the optical magnification of the microscope 10 corresponding to the observation magnification is also roughly determined. Under such circumstances, by using the microscope 10 according to this embodiment, the magnification adjustment device 70 can appropriately adjust the optical magnification of the microscope 10 in response to switching between multiple observation methods. Specifically, for example, when the optical magnification of the microscope 10 differs from the predetermined magnification for the switched observation method, the magnification adjustment device 70 may adjust the optical magnification of the microscope 10 closer to the predetermined magnification, or more preferably, change the optical magnification of the microscope 10 to the predetermined magnification. By appropriately setting the predetermined magnification for each observation method, embryologists do not need to switch the observation magnification through a separate operation from the operation of switching between observation methods, thereby simplifying microscope operation during ICSI.
[0018] Furthermore, in the microscope 10, the objective lens 40 is shared by multiple observation methods, and the optical magnification of the microscope 10 is adjusted by a magnification adjustment device 70 located on the image side of the objective lens 40. In other words, the objective lens 40 does not need to be switched when switching observation methods. This prevents problems such as focus shifts and shifts in the center of the field of view that would otherwise occur when switching the objective lens 40, thereby reducing the amount of adjustment work that needs to be done after switching between observation methods and observation magnifications.
[0019] In this way, the microscope 10 can simplify the work required to switch the observation method and observation magnification, as well as the adjustment work after switching. Therefore, the microscope 10 allows quick switching between the observation method and observation magnification, and allows quick start of specimen observation using the switched observation method.
[0020] A specific example of the configuration of the microscope system 1 will be described in detail below with reference to Figures 1 to 4. As shown in Figure 1, the microscope system 1 includes a microscope 10, a microscope controller 2 that controls the microscope 10, and an input device 3 for switching between observation methods. As shown in Figure 1, the microscope system 1 may further include a computer 4 that outputs images acquired by the microscope 10.
[0021] The microscope controller 2 is a control device that controls the microscope 10 in response to operations performed by an embryologist using the input device 3 and the computer 4. The microscope controller 2 may, for example, control the rotation of the turret of the universal capacitor 29 and the turret of the magnification adjustment device 70 included in the microscope 10, or may control the light emission of the light source device 21. The microscope controller 2 may output images acquired by the microscope 10 to the computer 4, or may output them to a monitor provided instead of the computer 4.
[0022] The input device 3 is a hand switch device for changing settings related to the observation method and observation magnification. For example, as shown in FIG. 3, the input device 3 has five buttons (buttons B1 to B5) corresponding to each of a plurality of observation methods. In the microscope system 1, pressing a button on the input device 3 rotates the turret of the universal condenser 29 and the turret of the magnification adjustment device 70, and the settings related to the observation method and observation magnification change according to the button that was pressed. Therefore, the embryologist can quickly switch settings related to the observation method and observation magnification simply by pressing one of these buttons.
[0023] The computer 4 includes at least a processor and a memory. The computer 4 may be a general-purpose device such as a personal computer, or may be a computer dedicated to the microscope system 1. As shown in Fig. 1, the computer 4 may be equipped with a monitor, and may display images acquired by the microscope 10 on the monitor.
[0024] The microscope system 1 does not necessarily have to include the computer 4. The computer 4 is not necessarily required, and the image acquired by the microscope 10 may be displayed on a monitor connected to the microscope controller 2. The microscope system 1 does not necessarily have to include a monitor, and the embryologist may visually observe the sample through an eyepiece tube 80 (described below) provided on the microscope 10 and operate the input device 3. The computer 4 may also have the function of the input device 3, and instructions input to the microscope controller 2 by operating the above-mentioned input device 3 may be input from the computer 4 to the microscope controller 2.
[0025] The microscope system 1 may be equipped with a manipulator including a pair of pipettes (pipette 7, pipette 8) operated with left and right handles (handle 5, handle 6) as shown in Figure 1. The manipulator is used to assist the embryologist in the ICSI procedure.
[0026] The microscope 10 is an inverted microscope equipped with a transmitted illumination system 20 above a stage 30. A revolver 45 is fitted with a plurality of objective lenses 40 which, in combination with an imaging lens 60, form an optical image of the sample. The microscope 10 further comprises an eyepiece tube 80 and an imaging device 90, enabling both visual observation and digital photography of the sample.
[0027] As will be described later, the microscope 10 is provided with a modulation optical element for visualizing an unstained phase object, which can be inserted into and removed from both the illumination light path and the observation light path. By inserting and removing a modulation optical element according to the observation method into and from the light path, the embryologist can observe the phase object using the microscope 10 while switching between multiple observation methods.
[0028] The microscope 10 is compatible with five observation methods: bright-field observation, relief contrast observation, differential interference contrast observation, phase contrast observation, and polarized light observation. However, the observation methods compatible with the microscope 10 are not limited to the above examples and may include other observation methods such as fluorescence observation and dark-field observation. Furthermore, for use in ICSI, the microscope 10 is preferably compatible with at least bright-field observation, relief contrast observation, differential interference contrast observation, or phase contrast observation, and even more preferably with polarized light observation. In ICSI, bright-field observation is used to position samples and pipettes using low-magnification objective lenses, such as 4x or 10x. Furthermore, relief contrast observation is used to observe egg morphology and confirm sperm motility (specifically, whether they swim quickly and straight) using objective lenses with magnifications such as 20x or 40x. Differential interference contrast observation is used to observe sperm using a high magnification objective lens, such as 60x, to see if there are any defects in the sperm head, while polarized light observation is used to observe the polarized spindles that appear in mature eggs using a 20x or 40x objective lens.
[0029] The transmitted illumination system 20 illuminates a sample placed on a stage 30 from above the stage 30. As shown in Figures 1 and 2, the transmitted illumination system 20 includes a light source device 21 and a universal condenser 29. Furthermore, as shown in Figure 2, the transmitted illumination system 20 includes a polarizer 22 and a compensator 23 between the light source device 21 that emits illumination light and the universal condenser 29.
[0030] The light source device 21 may include, for example, an LED (Light Emitting Diode) light source or a halogen lamp. The polarizer 22 is a modulation optical element that extracts linearly polarized light having a specific vibration direction, and is used in the microscope 10 mainly in relief contrast observation, differential interference observation, and polarization observation. In bright-field observation (and phase-contrast observation), the polarizer 22 may be removed from the optical path. The polarizer 22 is rotatably arranged in the microscope 10 so as to change its vibration direction relative to the vibration directions of the analyzer 61 (see FIG. 2) and polarizing plate 25a (see FIG. 2), which will be described later.
[0031] The compensator 23 is a modulating optical element used to measure retardation caused by birefringence of the sample. The compensator 23 is, for example, a Senarmont compensator, a liquid crystal modulator, or a Blais-Koehler compensator. In the microscope 10, the compensator 23 is used in polarized light observation to adjust the contrast of the image by changing the retardation caused by the compensator 23. In bright-field observation, relief contrast observation, and differential interference observation (and phase contrast observation), the compensator 23 may be removed from the optical path.
[0032] 2, the universal condenser 29 includes a plurality of modulation optical elements housed in a turret and a condenser lens 28. The plurality of modulation optical elements include a modulator 25 for the relief contrast observation method, a differential interference contrast (DIC) prism 26, and a ring slit plate 27. These plurality of modulation optical elements and aperture plate 24 are switched and used according to the observation method by rotating the turret.
[0033] The aperture plate 24 is a so-called empty hole in the turret, and indicates a turret slot in which no modulation optical element is arranged. The aperture plate 24 is used in bright-field observation and polarized light observation. The modulator 25 is a combination of a rectangular slit plate 25b having a rectangular slit formed therein and a polarizing plate 25a arranged to cover part of the slit. The modulator 25 is used in relief contrast observation. The DIC prism 26 is used in differential interference observation. The ring slit plate 27 having a ring-shaped slit formed therein is used in phase contrast observation. The modulator 25, DIC prism 26, and ring slit plate 27 are inserted into or removed from the pupil plane (entrance pupil, front focal position) of the condenser lens 28 by, for example, rotating the turret.
[0034] 2, a plurality of objective lenses 40 (objective lenses 41, 42, and 43) are provided below the stage 30 so as to be switchable by a revolver 45. These objective lenses 40 form an optical image of the sample in combination with an imaging lens 60. A relay lens 62 and an analyzer 61 are further provided on the optical path on the image side of the imaging lens 60.
[0035] The analyzer 61 is a modulation optical element that extracts linearly polarized light having a specific vibration direction, similar to the polarizer 22. In the microscope 10, the analyzer 61 is primarily used for differential interference contrast observation and polarized light observation. In bright-field observation and relief contrast observation (and phase-contrast observation), the analyzer 61 may be removed from the optical path, or the orientation of the polarizer 22 or the analyzer 61 may be adjusted so that the polarizer 22 and the analyzer 61 are in a parallel Nicol relationship. The analyzer 61 may be rotatably arranged in the microscope 10, similar to the polarizer 22, in order to change its vibration direction relative to the vibration direction of the polarizer 22. The analyzer 61 may be provided in an optical unit included in the magnification adjustment device 70 (described later). For example, the analyzer 61 may be provided in the optical unit 71, which is an optical unit compatible with polarized light observation, and the optical unit 74, which is an optical unit compatible with differential interference contrast observation.
[0036] At least one of the objective lenses 40 is shared by multiple observation methods. The objective lens shared by multiple observation methods is not particularly limited. Hereinafter, an example will be described in which an objective lens with a magnification of 20x (e.g., objective lens 41) is shared by multiple observation methods. However, multiple shared objective lenses may be attached to the revolver 45. In this example, objective lens 41 is a 20x objective lens with a numerical aperture of 0.7. However, instead of objective lens 41, for example, objective lens 42, which is a 10x objective lens with a numerical aperture of 0.7, may be shared by multiple observation methods. A numerical aperture of 0.7 is a numerical aperture that provides sufficient resolving power even when observing the morphology of sperm (e.g., the inside of a sperm head) at a magnification of 60x or more.
[0037] As shown in FIG. 2, the magnification adjustment device 70 includes multiple optical units (optical unit 71, optical unit 72, optical unit 73, optical unit 74, optical unit 75) corresponding to multiple observation methods, and a turret which is a switching device for switching between the multiple optical units.
[0038] The optical unit 71 is an optical unit compatible with polarized light observation and is inserted into the optical path when observing a sample using polarized light (PO) observation. The optical unit 71 includes an optical system 71a for adjusting the optical magnification of the microscope 10. The magnification of the optical system 71a is predetermined so that the optical magnification of the microscope 10 is a predetermined magnification frequently used in polarized light observation during ICSI. Specifically, polarized light observation is used to confirm the spindle of an ovum, as described below. Therefore, the predetermined magnification for polarized light observation is, for example, 20x, which is suitable for observing the structure of an ovum, as shown in FIG. 4. Therefore, if a 20x objective lens 40 is commonly used for multiple observation methods, the magnification of the optical system 71a is 1x. The optical unit 71 may further include an analyzer. In this case, the analyzer 61 between the magnification adjustment device 70 and the mirror 63 may be omitted. By including the analyzer in the optical unit 71 and omitting the analyzer 61, brighter observation becomes possible in observation methods that do not require an analyzer (bright-field observation, relay contrast observation, phase-contrast observation).
[0039] The optical unit 72 is an optical unit compatible with bright-field observation and is inserted into the optical path when observing a sample using bright-field (BF) observation. The optical unit 72 includes an optical system 72a for adjusting the optical magnification of the microscope 10. The magnification of the optical system 72a is predetermined so that the optical magnification of the microscope 10 is a predetermined magnification frequently used in bright-field observation for ICSI. Specifically, as will be described later, bright-field observation is used for searching for a drop in a petri dish, positioning a pipette, and the like. For this reason, the predetermined magnification for bright-field observation is relatively low to ensure a wide field of view, such as 10x, as shown in Figure 4. Therefore, if a 20x objective lens 40 is commonly used for multiple observation methods, the magnification of the optical system 72a is 0.5x, which is less than 1x.
[0040] The optical unit 73 is an optical unit compatible with the relief contrast observation method and is inserted into the optical path when observing a sample using the relief contrast (RC) observation method. The optical unit 73 includes an optical system 73a for adjusting the optical magnification of the microscope 10 and a modulator 73b for the relief contrast observation method. The magnification of the optical system 73a is predetermined so that the optical magnification of the microscope 10 is a predetermined magnification frequently used in the relief contrast observation method for ICSI. Specifically, the relief contrast observation method, as described below, is used to confirm the overall shape and motility of sperm, as well as the first polar body of an egg. For this reason, the predetermined magnification for the relief contrast observation method is, for example, 20x, which is suitable for observing the structure of an egg and the motility of sperm, as shown in FIG. 4. Therefore, if a 20x objective lens 40 is commonly used for multiple observation methods, the magnification of the optical system 73a is 1x. The modulator 73b includes three regions with different transmittances (for example, a region with a transmittance of approximately 100%, a region with a transmittance of approximately 5%, and a region with a transmittance of approximately 0%). The modulator 73b is a modulation optical element that forms a pair with the modulator 25 housed in the universal condenser 29, and is used together with the modulator 25 in the relief contrast observation method.
[0041] The optical unit 74 is compatible with differential interference contrast (DIC) observation and is inserted into the optical path when observing a sample using DIC observation. The optical unit 74 includes an optical system 74a for adjusting the optical magnification of the microscope 10 and a DIC prism 74b. The magnification of the optical system 74a is predetermined so that the optical magnification of the microscope 10 is a predetermined magnification frequently used in differential interference contrast observation during ICSI. Specifically, as described below, differential interference observation is used to observe empty capsules within sperm. For this reason, the predetermined magnification for differential interference observation is relatively high, e.g., 60x, as shown in Figure 4, which is suitable for observing the structure of sperm. Therefore, if a 20x objective lens 40 is commonly used for multiple observation methods, the magnification of the optical system 74a is 3x, which is greater than 1x. The DIC prism 74b is a modulation optical element that forms a pair with the DIC prism 26 housed in the universal condenser 29, and is used together with the DIC prism 26 in differential interference contrast observation. The optical unit 74 may further include an analyzer, in which case the analyzer 61 between the magnification adjustment device 70 and the mirror 63 may be omitted. Including the analyzer in the optical unit 74 and omitting the analyzer 61 enables brighter observation in observation methods that do not require an analyzer (bright-field observation, relay contrast observation, and phase-contrast observation).
[0042] The optical unit 75 is compatible with phase contrast observation and is inserted into the optical path when observing a sample using phase contrast (PC) observation. The optical unit 75 includes an optical system 75a for adjusting the optical magnification of the microscope 10 and a phase plate 75b. The magnification of the optical system 75a is predetermined so that the optical magnification of the microscope 10 is a predetermined magnification frequently used in phase contrast observation during ICSI. Specifically, phase contrast observation, like differential interference observation, is used to observe empty capsules within sperm. For this reason, the predetermined magnification for phase contrast observation is relatively high, e.g., 60x, as shown in Figure 4, which is suitable for observing sperm structure. Therefore, if a 20x objective lens 40 is commonly used for multiple observation methods, the magnification of the optical system 75a is 3x, which is greater than 1x. The phase plate 75b is a modulation optical element paired with the ring slit plate 27 housed in the universal condenser 29 and is used together with the ring slit plate 27 in phase contrast observation.
[0043] As described above, each of the optical units includes at least one of an optical system and a modulation optical element according to the observation method corresponding to that optical unit. The optical system included in the optical unit has a magnification according to the magnification ratio (predetermined magnification / magnification of objective lens) between the magnification of objective lens 40 and a predetermined magnification for the observation method corresponding to that optical unit.
[0044] In this example, optical unit 71 and optical unit 72 include only an optical system. That is, the housings of optical unit 71 and optical unit 72 each house only an optical system. Furthermore, optical unit 73, optical unit 74, and optical unit 75 include both an optical system and a modulation optical element. That is, the housings of optical unit 73, optical unit 74, and optical unit 75 each house both an optical system and a modulation optical element. However, the multiple optical units may include an optical unit that includes only a modulation optical element, and each of the multiple optical units may include a housing that houses at least one of an optical system and a modulation optical element.
[0045] The magnification adjustment device 70 is disposed between the imaging lens 60, which is disposed on the image side of the objective lens 40, and the eyepiece tube 80 (and the imaging device 90). Specifically, the magnification adjustment device 70 is disposed between the relay lens 62 and the mirror 63 so that the pupil modulation elements (modulator 73b, DIC prism 74b, phase plate 75b, etc.) included in the optical unit can be disposed on a plane optically conjugate with the pupil plane (exit pupil, back focal position) of the objective lens 40. The mirror 63 is disposed so as to be insertable into and removable from the optical path and is used to switch between visual observation and digital photography. More specifically, the magnification adjustment device 70 is disposed between the relay lens 62 and the analyzer 61 so that the DIC prism 74b included in the optical unit 74 is inserted into the optical path between the polarizer 22, which is disposed on the illumination optical path, and the analyzer 61, which is disposed on the observation optical path. With this arrangement, the magnification adjustment device 70 adjusts the optical magnification of the microscope 10 on the optical path closer to the image side than the imaging lens 60.
[0046] The magnification adjustment device 70 configured as described above uses a switching device to switch the optical units placed on the optical path depending on the observation method. This allows the magnification adjustment device 70 to adjust the optical magnification of the microscope 10 on the optical path closer to the image than the imaging lens 60, and to switch between multiple observation methods. In other words, by switching between multiple optical units, the magnification adjustment device 70 can switch between multiple observation methods and adjust the optical magnification of the microscope 10 at the same time.
[0047] The magnifications described above for the optical systems included in the multiple optical units are merely examples. Any magnification suitable for the observation target and purpose of each observation method may be used. For example, the predetermined magnification (first predetermined magnification) for bright-field observation may be lower than the predetermined magnification (second predetermined magnification) for differential interference contrast observation or phase contrast observation. Therefore, the magnification of the optical system 72a may be lower than the magnification of the optical system 74a or the optical system 75a. Furthermore, for example, the predetermined magnification (third predetermined magnification) for relief contrast observation may be higher than the predetermined magnification (first predetermined magnification) for bright-field observation and lower than the predetermined magnification (second predetermined magnification) for differential interference contrast observation or phase contrast observation. Therefore, the magnification of the optical system 73a may be higher than the magnification of the optical system 72a and lower than the magnification of the optical system 74a or the optical system 75a. Furthermore, for example, the predetermined magnification (fourth predetermined magnification) for polarization observation may be higher than the predetermined magnification (first predetermined magnification) for bright-field observation and lower than the predetermined magnification (second predetermined magnification) for differential interference observation or phase-contrast observation. More specifically, the predetermined magnification (fourth predetermined magnification) for polarization observation may be equal to the predetermined magnification (third predetermined magnification) for relief contrast observation. Therefore, the magnification of optical system 71a may be higher than the magnification of optical system 72a and lower than the magnification of optical system 74a or optical system 75a, and may be equal to the magnification of optical system 73a.
[0048] Furthermore, although an example has been shown in which the magnification adjustment device 70 adjusts the optical magnification of the microscope 10 from 10x to 60x, this adjustment range of the optical magnification is merely one example. The magnification ratio between the upper and lower limits of the optical magnification may be less than the above-mentioned 6x. However, it is sufficient that the optical magnification is adjusted so that various observation targets in ICSI can be appropriately observed. To this end, it is desirable that the magnification adjustment device 70 adjust the optical magnification within an adjustment range in which the magnification ratio between the upper and lower limits of the optical magnification is 3x or more.
[0049] As described above, the magnification adjustment device 70 desirably adjusts the optical magnification of the microscope 10 from a magnification lower than that of the objective lens 40 (10x in this example) to a magnification higher than that of the objective lens 40 (60x in this example). Specifically, the magnification adjustment device 70 desirably adjusts the optical magnification of the microscope 10 to a magnification that enables observation of a range wider than the range on the specimen surface determined by the magnification of the objective lens 40 and the objective lens's OFN (Objective Field Number) (for example, Φ1.1 mm for a 20x objective lens with an OFN of 22), in response to switching to a predetermined observation method. More specifically, the magnification adjustment device 70 desirably performs intermediate magnification changes of 1x or less in response to switching to bright-field observation, for example. This makes it possible to ensure a wide field of view while using an objective lens with sufficient resolving power in common for multiple observation methods.
[0050] Eyepiece tube 80 and imaging device 90 are located after mirror 63, which switches between visual observation and digital photography. Inserting mirror 63 into the optical path directs light to eyepiece tube 80, and removing mirror 63 from the optical path directs light to imaging device 90. Eyepiece tube 80 includes an eyepiece lens 81. Imaging device 90 also includes an adapter lens 91 and imaging element 92. Imaging element 92 is, for example, a CCD (Charge Coupled Device) image sensor or a CMOS (Complementary Metal-Oxide-Semiconductor) image sensor.
[0051] In the above description, it is assumed that the magnification of the eyepiece 81 and the adapter lens 91 is 1x, but there are no particular limitations on the magnification of the eyepiece 81 and the adapter lens 91. Because the magnification of the eyepiece 81 (adapter lens 91) affects the optical magnification of the microscope 10, the magnification adjustment device 70 should adjust the optical magnification taking into account the magnification of the eyepiece 81 (adapter lens 91).
[0052] Furthermore, as shown in FIG. 2, the microscope 10 may include a laser-assisted hatching unit 50. The laser-assisted hatching unit 50 irradiates a sample with laser light by introducing the laser light into the optical path between the objective lens 40 and the imaging lens 60. More specifically, the laser-assisted hatching unit 50 is used, for example, to irradiate the zona pellucida surrounding an embryo with laser light to thin or incise a portion of the zona pellucida so that the embryo can implant after developing from a fertilized egg. The laser-assisted hatching unit 50 includes a splitter 51, a scanner 52, a lens 53, and a laser 54. The splitter 51 is, for example, a dichroic mirror. The scanner 52 is, for example, a galvanometer scanner, and adjusts the irradiation position of the laser light in a direction perpendicular to the optical axis of the objective lens 40. The lens 53 converts the laser light into a parallel beam.
[0053] Fig. 5 is a flowchart showing an example of the procedure for ICSI. Hereinafter, the procedure for ICSI performed by an embryologist using the microscope system 1 described above and the operation of the microscope system 1 during ICSI will be specifically described with reference to Fig. 5.
[0054] First, the embryologist prepares a sample (step S1). Here, the embryologist creates a sample containing multiple drops in a petri dish, for example, and places it on the stage 30. The multiple drops include a cleaning drop used to clean a pipette, a sperm suspension drop containing sperm, and an egg manipulation drop containing eggs. These drops are covered with, for example, mineral oil.
[0055] Next, the embryologist sets up the microscope system 1 (step S2). Here, the embryologist, for example, presses button B1 on the input device 3 to change the observation method and observation magnification settings of the microscope system 1. The microscope controller 2, detecting the pressing of button B1, controls the microscope 10 to change the observation method to brightfield observation and the optical magnification of the microscope 10 to 10x. More specifically, the microscope 10 rotates the turret of the universal condenser 29 so that the aperture plate 24 is positioned on the optical path, and further rotates the turret of the magnification adjustment device 70 so that the optical unit 72 is positioned on the optical path. The embryologist then operates handles 5 and 6 to adjust the positions of the pipettes 7 and 8 and focus on the pipettes 7 and 8. Furthermore, the stage 30 is moved to wash the pipettes 7 and 8 with cleaning drops. During bright-field observation, it is desirable to adjust the polarizer 22 or the analyzer 61 so that they are in a parallel Nicol relationship. However, if the analyzer 61 between the magnification adjustment device 70 and the mirror 63 is omitted and an analyzer is included in each of the optical units 71 and 74, there is no need to adjust the polarizer and analyzer so that they are in a parallel Nicol relationship.
[0056] Once the setup is complete, the embryologist selects the sperm (steps S3 to S6). First, the embryologist selects high-quality sperm based on morphology and motility (step S3). Here, the embryologist, for example, presses button B2 on the input device 3 to change the observation method and observation magnification settings of the microscope system 1. Upon detecting the pressing of button B2, the microscope controller 2 controls the microscope 10 to change the observation method to relief contrast observation and the optical magnification of the microscope 10 to 20x. More specifically, the microscope 10 rotates the turret of the universal condenser 29 so that the modulator 25 is positioned on the optical path, and then rotates the turret of the magnification adjustment device 70 so that the optical unit 73 is positioned on the optical path. The embryologist then moves the stage 30 to move the observation position to the sperm-suspended drop, focuses on the sperm in the sperm-suspended drop, and selects high-quality sperm suitable for fertilization. In this case, the quality of the sperm is judged based on the morphology and motility of the shaded sperm using the relief contrast observation method, and good sperm are selected based on this judgment. At this time, it is desirable to rotate the polarizer 22 to adjust the contrast.
[0057] Once the good sperm have been selected based on their morphology and motility, the embryologist immobilizes them (step S4). Here, the embryologist uses a pipette to rub the tails of the good sperm against the bottom of the petri dish, damaging and immobilizing them. This step, like step S3, is performed using the relief contrast observation method at 20x magnification.
[0058] The embryologist then further selects the high-quality sperm based on the internal structure of the immobilized high-quality sperm (step S5). Here, the embryologist, for example, presses button B4 on the input device 3 to change the observation method and observation magnification settings of the microscope system 1. Upon detecting the pressing of button B4, the microscope controller 2 controls the microscope 10 to change the observation method to differential interference contrast observation and the optical magnification of the microscope 10 to 60x. More specifically, the microscope 10 rotates the turret of the universal condenser 29 so that the DIC prism 26 is positioned in the optical path, and further rotates the turret of the magnification adjustment device 70 so that the optical unit 74 is positioned in the optical path. The embryologist then closely observes the heads of the immobilized high-quality sperm and selects high-quality sperm suitable for fertilization. Here, the quality of the sperm is judged based on the size of the empty cells present in the heads visualized by differential interference contrast observation, and high-quality sperm are selected based on this judgment. Specifically, high-quality sperm with small empty cells are selected. During observation using differential interference contrast, the polarizer 22 or the analyzer 61 is adjusted so that the polarizer 22 and the analyzer 61 are in a crossed Nicol relationship.
[0059] In step S5, phase-contrast observation may be used instead of differential interference observation. In this case, the embryologist may change the observation method and observation magnification settings of the microscope system 1, for example, by pressing button B5 on the input device 3. Upon detecting the pressing of button B5, the microscope controller 2 controls the microscope 10 to change the observation method to phase-contrast observation and the optical magnification of the microscope 10 to 60x. More specifically, the microscope 10 rotates the turret of the universal condenser 29 so that the ring slit plate 27 is positioned on the optical path, and further rotates the turret of the magnification adjustment device 70 so that the optical unit 75 is positioned on the optical path. During observation using phase-contrast observation, the polarizer 22 or the analyzer 61 is adjusted so that they are in a parallel Nicol relationship.
[0060] The embryologist then takes the good sperm selected in step S5 into the injection pipette (pipette 7) (step S6), thereby completing the sperm selection process.
[0061] Once the selection of good sperm is complete, the embryologist checks the egg in preparation for sperm injection (steps S7 to S8). First, the embryologist checks the position of the egg's first polar body (step S7). Here, the embryologist, for example, presses button B2 on the input device 3 to change the observation method and observation magnification settings of the microscope system 1. Upon detecting the pressing of button B2, the microscope controller 2 controls the microscope 10 to change the observation method to the relief contrast observation method and the optical magnification of the microscope 10 to 20x. More specifically, the microscope 10 rotates the turret of the universal condenser 29 so that the modulator 25 is positioned on the optical path, and further rotates the turret of the magnification adjustment device 70 so that the optical unit 73 is positioned on the optical path. The embryologist then moves the stage 30 to move the observation position to the egg manipulation drop and focuses on the egg in the egg manipulation drop. Furthermore, the position of the first polar body of the oocyte is confirmed, and the holding pipette (pipette 8) is operated to change the orientation of the oocyte so that the first polar body is positioned at 12 o'clock or 6 o'clock. This is because there is a relatively high probability that the spindle confirmed in step S8 is present near the first polar body. In step S7 as well, it is desirable to rotate the polarizer 22 to adjust the contrast.
[0062] The embryologist then confirms the ovum spindle (step S8). Here, the embryologist, for example, presses button B3 on the input device 3 to change the observation method and observation magnification settings of the microscope system 1. The microscope controller 2, detecting the pressing of button B3, controls the microscope 10 to switch the observation method to polarized light observation and maintain the optical magnification of the microscope 10 at 20x. More specifically, the microscope 10 rotates the turret of the universal condenser 29 so that the aperture plate 24 is positioned on the optical path, and further rotates the turret of the magnification adjustment device 70 so that the optical unit 71 is positioned on the optical path. As a result, the microscope 10 switches the observation method but maintains the optical magnification unchanged. The embryologist then confirms the position of the ovum spindle and operates the holding pipette (pipette 8) to change the orientation of the ovum so that the spindle is positioned at 12 o'clock or 6 o'clock. This is to prevent damage to the spindle by the injection pipette that is thrust into the oocyte from the 3 o'clock or 9 o'clock direction in step S9, which will be described later. In step S8, it is desirable to adjust the polarizer 22 or the analyzer 61 so that the polarizer 22 and the analyzer 61 are in a crossed Nicol relationship.
[0063] Finally, the embryologist injects the sperm into the egg (step S9). Here, the embryologist, for example, presses button B2 on the input device 3 to change the observation method and observation magnification settings of the microscope system 1. Upon detecting the pressing of button B2, the microscope controller 2 controls the microscope 10 to switch the observation method to the relief contrast observation method while maintaining the optical magnification of the microscope 10 at 20x. More specifically, the microscope 10 rotates the turret of the universal condenser 29 so that the modulator 25 is positioned on the optical path, and then rotates the turret of the magnification adjustment device 70 so that the optical unit 73 is positioned on the optical path. As a result, the microscope 10 switches the observation method but maintains the optical magnification unchanged. The embryologist then fixes the egg by aspirating it with the holding pipette (pipette 8) and inserts the injection pipette (pipette 7) into the egg from the 3 o'clock or 9 o'clock direction. Finally, the good sperm is injected into the egg from the injection pipette (pipette 7), completing the series of steps. It is also desirable to adjust the contrast by rotating the polarizer 22 in step S9. After the series of steps shown in Figure 5 are completed, the embryologist returns the sperm-injected egg to the incubator for incubation.
[0064] As described above, with the microscope 10 and microscope system 1, when switching between observation methods, which frequently occurs during ICSI, the observation magnification can be simultaneously and appropriately adjusted simply by switching the observation method. This allows for quick switching to the desired combination of observation method and observation magnification. Furthermore, because the observation magnification is adjusted without switching the objective lens, misalignment of the focus or the center of the field of view is unlikely to occur. This allows subsequent work to be started quickly after switching, which also contributes to shortening the ICSI work time. Therefore, with the microscope 10 and microscope system 1, damage to germ cells can be minimized, improving the success rate of ICSI.
[0065] [Second embodiment] Fig. 6 is a diagram illustrating the configuration of a microscope 100. The microscope system according to this embodiment differs from the microscope system 1 in that it includes the microscope 100 shown in Fig. 6 instead of the microscope 10. In other respects, it is the same as the microscope system 1.
[0066] The main differences between microscope 100 and microscope 10 are that the arrangement of the analyzer and magnification adjustment device is different, that the microscope 100 does not include a configuration for phase contrast observation, and that the objective lens 44, which is used in common with multiple observation methods, includes a modulator 44a for relief observation. More specifically, the arrangement of the analyzer and magnification adjustment device differs from that of microscope 10 in that the analyzer used in polarization observation and differential interference observation is located within the magnification adjustment device, and that the magnification adjustment device is located between the objective lens 40a and the imaging lens 60. The following describes microscope 100, focusing on these differences.
[0067] If a pupil modulation element can be placed at the exit pupil position of the objective lens 40a, the microscope 100 and the microscope system including the microscope 100 can also simultaneously and appropriately adjust the observation magnification by simply switching the observation method when switching the observation method, which occurs frequently in ICSI, just like the microscope 10 and the microscope system 1. Therefore, the operation time for ICSI can be shortened. In this embodiment, a pupil modulation element, a modulator 44a for RC observation, is placed at the pupil position of the objective lens 44.
[0068] Magnification adjustment device 170 included in microscope 100 is similar to magnification adjustment device 70 in that it includes multiple optical units corresponding to multiple observation methods. Optical unit 171, optical unit 172, optical unit 173, and optical unit 174 are optical units corresponding to polarization observation, bright-field observation, relief contrast observation, and differential interference observation, respectively.
[0069] The optical unit 171 includes an analyzer 171b. The optical unit 172 includes an optical system 172a having a magnification of 0.5x. The optical unit 173 is an empty unit that does not include any optical elements or optical systems. The modulator 44a for the relief contrast observation method is disposed in the objective lens 44, not in the optical unit 173. The optical unit 174 includes an optical system 174a having a magnification of 3x, a DIC prism 174b, and an analyzer 174c.
[0070] In this way, the multiple optical units included in magnification adjustment device 170, except for optical unit 173, are similar to the multiple optical units included in magnification adjustment device 70 in that they include at least one of an optical system having a magnification corresponding to the magnification ratio between the magnification of objective lens 40a and a predetermined magnification for the observation method corresponding to that optical unit, and a modulation optical element corresponding to the observation method corresponding to that optical unit.
[0071] [Third embodiment] Fig. 7 is a diagram illustrating the configuration of a microscope 200. The microscope system according to this embodiment differs from the microscope system 1 in that it includes the microscope 200 shown in Fig. 7 instead of the microscope 10. In other respects, it is the same as the microscope system 1.
[0072] The microscope 200 differs from the microscope 10 in that it includes an observation method switching device 270 that switches between multiple observation methods, separate from the magnification adjustment device 280, does not include a configuration for phase-contrast observation, and the objective lens 44, which is used in common across multiple observation methods, includes a modulator 44a for relief observation. The microscope 200 is similar to the microscope 100 according to the second embodiment in that it does not include a configuration for phase-contrast observation and that the objective lens 44, which is used in common across multiple observation methods, includes a modulator 44a for relief observation. The observation method switching device 270 includes one or more modulation optical elements (analyzer 271, modulator 273), each of which is used in at least one of the multiple observation methods, and a turret that switches between them. The observation method switching device 270 switches between multiple observation methods by inserting or removing at least one of the one or more modulation optical elements into or from the optical path.
[0073] Specifically, when switching to polarization observation, the observation method switching device 270 simply inserts the analyzer 271 into the optical path and removes other modulation optical elements from the optical path. Furthermore, when switching to bright-field observation or relief contrast observation, the observation method switching device 270 simply removes modulation optical elements from the optical path. Furthermore, when switching to differential interference observation, the observation method switching device 270 simply inserts a modulator 273, which combines a DIC prism 273a and an analyzer 273b, into the optical path and removes other modulation optical elements from the optical path.
[0074] The microscope 200 also differs from the microscope 10 in that the magnification adjustment device 280 includes a variable magnification optical system. The variable magnification optical system included in the magnification adjustment device 280 has a structure that changes its own magnification. The variable magnification optical system may include, for example, a zoom lens that changes the magnification by moving some of the lenses in the variable magnification optical system in the optical axis direction, as shown in FIG. 7. The variable magnification optical system may also include, for example, a variable-focus lens that changes the focal length by changing the lens shape.
[0075] When the optical magnification of the microscope 200 differs from the predetermined magnification for the observation method after switching by the observation method switching device 270, the magnification adjustment device 280 changes the magnification of the microscope 200 by changing the magnification of the magnification adjustment device 280. Specifically, the microscope 200 may include an interlocking mechanism for mechanically interlocking the observation method switching device 270 and the magnification adjustment device 280, and the handle of the magnification adjustment device 280 may rotate to a predetermined position in response to rotation of the observation method switching device 270.
[0076] Furthermore, in a microscope system including the microscope 200, the microscope controller 2 may control the observation method switching device 270 and the magnification adjustment device 280, which may result in the observation method switching device 270 and the magnification adjustment device 280 working together. In other words, the microscope controller 2 may control the observation method switching device 270 and the magnification adjustment device 280 so that the switching between multiple observation methods by the observation method switching device 270 and the adjustment of the optical magnification by the magnification adjustment device 280 work together.
[0077] If a pupil modulation element can be placed at the exit pupil position of the objective lens 40a, the microscope 200 and the microscope system including the microscope 200, like the microscope 10 and the microscope system 1, can simultaneously and appropriately adjust the observation magnification by simply switching the observation method when switching the observation method, which occurs frequently in ICSI. Therefore, the operation time for ICSI can be shortened. In this embodiment, a pupil modulation element, a modulator 44a for RC observation, is placed at the pupil position of the objective lens 44.
[0078] [Fourth embodiment] Fig. 8 is a diagram illustrating the configuration of a microscope 300. The microscope system according to this embodiment differs from the microscope system according to the third embodiment in that it includes the microscope 300 shown in Fig. 8 instead of the microscope 200. In other respects, it is the same as the microscope system according to the third embodiment.
[0079] Microscope 300 is similar to microscope 200 shown in Fig. 7 in that it includes an observation method switching device and a magnification adjustment device. However, microscope 300 differs from microscope 200 in that observation method switching device 270 and magnification adjustment device 380 are arranged on the optical path closer to the image side than imaging lens 60. Also, like microscope 1 according to the first embodiment, microscope 300 differs from microscope 200 in that it includes a configuration for phase contrast observation, and that objective lens 41, which is used in common for multiple observation methods, does not include a modulator for relief observation. Note that magnification adjustment device 380 includes a variable magnification optical system having a structure that changes its own magnification.
[0080] The microscope 300 and the microscope system including the microscope 300 can also simultaneously and appropriately adjust the observation magnification simply by switching the observation method when switching between observation methods, which occurs frequently during ICSI. This allows the operation time for ICSI to be shortened.
[0081] [Fifth embodiment] Fig. 9 is a diagram illustrating the configuration of a microscope 400. The microscope system according to this embodiment differs from the microscope system according to the fourth embodiment in that it includes the microscope 400 shown in Fig. 9 instead of the microscope 300. In other respects, it is the same as the microscope system according to the fourth embodiment.
[0082] 8 in that it includes an observation method switching device and a magnification adjustment device on the optical path closer to the image than the imaging lens 60. However, in the microscope 400, the magnification adjustment device 480 includes one or more optical systems (optical system 481, optical system 482, optical system 483) each used for at least one of a plurality of observation methods, instead of a variable magnification optical system, and the optical magnification of the microscope 400 is adjusted by inserting or removing at least one of these one or more optical systems into or from the optical path, which is different from the microscope 300.
[0083] The microscope 400 and the microscope system including the microscope 400 can also simultaneously and appropriately adjust the observation magnification by simply switching the observation method when switching the observation method, which occurs frequently in ICSI. Therefore, the operation time for ICSI can be shortened.
[0084] [Sixth embodiment] Fig. 10 is a diagram illustrating the configuration of a microscope 500. The microscope system according to this embodiment differs from the microscope system according to the fifth embodiment in that it includes the microscope 500 shown in Fig. 10 instead of the microscope 400. In other respects, it is the same as the microscope system according to the fifth embodiment.
[0085] 9 in that it includes an observation method switching device and a magnification adjustment device. However, microscope 500 differs from microscope 400 in that it includes observation method switching device 270 and magnification adjustment device 580 on the optical path between objective lens 40 and imaging lens 60. Note that magnification adjustment device 580 includes one or more optical systems (optical system 581, optical system 582, optical system 583) each used for at least one of a plurality of observation methods, and like microscope 400, the optical magnification of microscope 500 is adjusted by inserting or removing at least one of these one or more optical systems into or from the optical path.
[0086] If a pupil modulation element (modulator 272, DIC prism 273a, phase plate 274) can be placed at the exit pupil position of the objective lens 40, the microscope 500 and the microscope system including the microscope 500 can also simultaneously and appropriately adjust the observation magnification by simply switching the observation method when switching the observation method, which occurs frequently in ICSI. Therefore, the operation time for ICSI can be shortened.
[0087] The above-described embodiments are illustrative examples provided to facilitate understanding of the invention, and the present invention is not limited to these embodiments. Modifications and alternatives to the above-described embodiments may be included. In other words, the components of each embodiment may be modified without departing from the spirit and scope of the invention. Furthermore, new embodiments can be implemented by appropriately combining multiple components disclosed in one or more embodiments. Furthermore, some components may be deleted from or added to the components shown in each embodiment. Furthermore, the order of the processing steps shown in each embodiment may be reversed as long as they are not inconsistent. In other words, the microscope of the present invention is susceptible to various modifications and alterations without departing from the scope of the claims.
[0088] Fig. 11 is a diagram illustrating the configuration of a universal condenser 600. In the above-described embodiment, an example was shown in which the polarizer 22 and compensator 23, which are placed on the illumination light path, are placed outside the turret of the universal condenser 29, but the polarizer 22 and compensator 23 may be included in the universal condenser 600 as shown in Fig. 11, and may be inserted into or removed from the light path as needed by a turret provided on the incident side of the condenser lens 601, similar to other modulation optical elements.
[0089] FIG. 11 shows a configuration in which an optical unit 610 used in polarization observation, an optical unit 620 used in bright-field observation, an optical unit 630 used in relief contrast observation, an optical unit 640 used in differential interference observation, and an optical unit 650 used in phase-contrast observation can be switched using a turret on a universal condenser 600.
[0090] The optical unit 610 houses an aperture plate 613 together with a polarizer 611 and a compensator 612. The optical unit 620 houses an aperture plate 621. The optical unit 630 houses a polarizer 631 and a modulator 632. The modulator 632 is composed of a polarizing plate 632a and a rectangular slit plate 632b. The polarizer 631 is housed in the polarizer 631 so as to be rotatable so as to change the vibration direction of the polarizer 631 relative to the vibration direction of the polarizing plate 632a. The optical unit 640 houses a polarizer 641 and a DIC prism 642. The optical unit 650 houses a ring slit plate 651.
[0091] Fig. 12 is a diagram illustrating the configuration of the magnification adjustment device 700. Fig. 1 shows an example in which the analyzer 61 placed on the observation light path is placed outside the turret of the magnification adjustment device, but the analyzer 61 may be included in the magnification adjustment device as shown in Fig. 12, and may be inserted into or removed from the light path as needed by the turret of the magnification adjustment device, similar to other modulation optical elements.
[0092] FIG. 12 shows a configuration in which an optical unit 710 used in polarization observation, an optical unit 720 used in bright-field observation, an optical unit 730 used in relief contrast observation, an optical unit 740 used in differential interference observation, and an optical unit 750 used in phase-contrast observation can be switched using a turret of a magnification adjustment device 700.
[0093] The optical unit 710 houses an analyzer 711 together with an optical system 712. The optical unit 720 houses an optical system 721. The optical unit 730 houses a modulator 731 and an optical system 732. The optical unit 740 houses an analyzer 741, a DIC prism 742, and an optical system 743. The optical unit 750 houses a phase plate 751 and an optical system 752.
[0094] FIG. 13 illustrates the configuration of a microscope system 1a. The microscope system 1a differs from the microscope system 1 shown in FIG. 1 in that it includes a microscope 800 instead of the microscope 10. The microscope 800 is an upright microscope that includes the universal condenser 600 shown in FIG. 11 and the magnification adjustment device 700 shown in FIG. 12 on the illumination and observation optical paths, respectively. The microscope 800 extracts near-infrared light from illumination light emitted from a light source device 801 using a bandpass filter 802, and irradiates the sample with the universal condenser 600, which then passes through a collector lens 804. The embryologist may visually observe the optical image of the sample formed via an objective lens 805, an imaging lens 806, and the magnification adjustment device 700, through an eyepiece 807, or may view an image of the sample captured by an imaging device 808 on the monitor of a computer 4. The microscope 800 allows the observation method and observation magnification to be changed by switching the magnification adjustment device 700 and the universal condenser 600 in conjunction with each other.
[0095] While the above-described embodiment illustrates an inverted microscope, the present invention may also be applied to an upright microscope, as shown in FIG. 13 , and similar effects can be achieved in this case. While the above-described embodiment illustrates an example in which optical elements and optical systems are switched using a turret, other switching means, such as a slider, may be used to switch the optical elements and optical systems. While the above-described embodiment illustrates an example in which the observation method and observation magnification are switched in conjunction with each other, the amount of illumination light emitted from the light source device may also be adjusted in conjunction with these. Specifically, the microscope controller 2, which functions as a light source control device, may adjust the amount of illumination light emitted from the light source device 21 in response to switching between multiple observation methods. For example, the microscope controller 2 may control the amount of light to be increased in polarization observation or differential interference observation, in which the polarizer 22 and the analyzer 61 are adjusted to have a crossed Nicol relationship, because images tend to be dark. [Explanation of symbols]
[0096] 1, 1a... Microscope system, 10, 100, 200, 300, 400, 500, 800... Microscope, 40, 41, 42, 43... Objective lens, 70, 170, 280, 380, 480, 580, 700... Magnification adjustment device, 270... Observation method switching device
Claims
1. A microscope used with multiple observation methods, an objective lens that is commonly used in the plurality of observation methods; a magnification adjusting means arranged on the image side of the objective lens and adapted to adjust the optical magnification of the microscope in accordance with switching between the plurality of observation methods without switching between the objective lens, The magnification adjustment means is an optical system having a magnification corresponding to a magnification ratio between the magnification of the objective lens and a predetermined magnification for the observation method; If the optical magnification of the microscope is different from a predetermined magnification for the observation method after switching, the optical magnification of the microscope is changed to the predetermined magnification by adjusting the magnification of the optical system. A microscope characterized by:
2. 2. The microscope according to claim 1, the magnification adjustment means includes a plurality of optical units corresponding to the plurality of observation methods, Each of the plurality of optical units is the optical system; a modulation optical element according to an observation method corresponding to the optical unit, At least one of the plurality of optical units includes the optical system, The magnification adjusting means switches between the plurality of optical units, thereby simultaneously switching between the plurality of observation methods and adjusting the optical magnification. A microscope characterized by:
3. 3. The microscope according to claim 2, Each of the plurality of optical units further includes a housing that collectively houses at least one of the optical system and the modulation optical element included in the optical unit. A microscope characterized by:
4. 4. The microscope according to claim 3, the plurality of optical units include a first optical unit corresponding to a bright-field observation method, a second optical unit corresponding to a relief contrast observation method, and a third optical unit corresponding to a phase-contrast observation method or a differential interference observation method; the first optical unit includes an optical system having a magnification of less than 1x; the second optical unit includes a modulation optical element used in the relief contrast observation method, The third optical unit includes an optical system having a magnification of more than 1 and a modulation optical element used in the phase contrast observation method or the differential interference observation method. A microscope characterized by:
5. 5. The microscope according to claim 4, the plurality of optical units further includes a fourth optical unit corresponding to a polarization observation method; The fourth optical unit includes a modulation optical element used in the polarization observation method. A microscope characterized by:
6. The microscope according to claim 1, further comprising: and a switching means for switching between the plurality of observation methods by inserting or removing at least one of the one or more modulation optical elements into or from the optical path, each of the one or more modulation optical elements being used in at least one of the plurality of observation methods. A microscope characterized by:
7. 7. The microscope according to claim 6, The magnification adjusting means includes one or more optical systems each used in at least one of the plurality of observation methods, and changes the optical magnification to the predetermined magnification by inserting or removing at least one of the one or more optical systems into or from the optical path. A microscope characterized by:
8. 7. The microscope according to claim 6, The optical system includes a variable magnification optical system having a structure for changing its own magnification, and the optical magnification is changed to the predetermined magnification by changing the magnification of the variable magnification optical system. A microscope characterized by:
9. 9. The microscope according to claim 8, The variable magnification optical system includes a zoom lens. A microscope characterized by:
10. 10. The microscope according to claim 6, A linking mechanism is provided to mechanically link the switching means and the magnification adjusting means. A microscope characterized by:
11. The microscope according to any one of claims 6 to 9, further comprising: a control device for controlling the magnification adjustment means and the switching means, The control device controls the magnification adjustment means and the switching means so that the switching of the plurality of observation methods by the switching means and the adjustment of the optical magnification by the magnification adjustment means are linked. A microscope characterized by:
12. The microscope according to any one of claims 1 to 11, the plurality of observation methods include at least a bright field observation method, a relief contrast observation method, and a phase contrast observation method or a differential interference observation method; the first predetermined magnification for the bright-field observation method is lower than the second predetermined magnification for the phase-contrast observation method or the differential interference contrast observation method; The third predetermined magnification for the relief contrast observation method is higher than the first predetermined magnification and lower than the second predetermined magnification. A microscope characterized by:
13. 13. The microscope according to claim 12, the plurality of observation methods further includes a polarization observation method, The fourth predetermined magnification for the polarization observation method is equal to the third predetermined magnification. A microscope characterized by:
14. The microscope according to any one of claims 1 to 13, The magnification adjusting means adjusts the optical magnification within an adjustment range in which the magnification ratio between the upper limit value and the lower limit value of the optical magnification is 3 times or more. A microscope characterized by:
15. 15. The microscope according to claim 1, The magnification adjusting means adjusts the optical magnification to a magnification that allows observation of a range wider than the range on the specimen surface determined by the magnification of the objective lens and the OFF-field noise (OFFN) of the objective lens, in accordance with switching to a predetermined observation method. A microscope characterized by:
16. The microscope according to any one of claims 1 to 15, further comprising: an imaging lens disposed on the image side of the objective lens; The magnification adjusting means adjusts the optical magnification on the optical path between the image side and the imaging lens. A microscope characterized by:
17. The microscope according to any one of claims 1 to 15, further comprising: an imaging lens disposed on the image side of the objective lens; The magnification adjusting means adjusts the optical magnification on the optical path between the objective lens and the imaging lens. A microscope characterized by:
18. The microscope according to any one of claims 1 to 17, further comprising: a light source device that emits illumination light; a light source control device that controls the amount of illumination light emitted from the light source device in accordance with switching between the plurality of observation methods; A microscope characterized by:
19. 19. The microscope according to claim 1, The microscope is an inverted microscope A microscope characterized by:
20. 2. The microscope according to claim 1, The magnification of the objective lens is constant A microscope characterized by:
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