Microscope system

Abstract

A microscope system 1 comprises: a microscope 100 comprising a gel immersion objective lens 130 in which gel is attached to a tip part, a stage 110 on which an object 10 to be observed is mounted, and a revolver 120 that is a focusing device for changing the distance between the gel immersion objective lens 130 and the stage 110 in the direction of an optical axis; and a control device 200 that controls the microscope 100. The control device 200 acquires close contact time information relating to a close contact time, which is a duration of a close contact state of close contact with the object 10 to be observed, and when the gel immersion objective lens 130 is retracted before the close contact time exceeds a predetermined time, controls the focusing device such that the gel immersion objective lens 130 is retracted at a speed corresponding to the close contact time.

Description

Microscope system

[0001] The disclosure of this specification relates to a microscope system.

[0002] An objective lens for a microscope (hereinafter referred to as a gel-immersion objective lens) with a gel attached to the tip instead of an immersion liquid such as water or oil is superior in maintenance and workability compared to an immersion objective lens that uses an immersion liquid, and is expected to improve the efficiency of microscope observation. Related technologies are described in, for example, Patent Document 1.

[0003] U.S. Patent Application Publication No. 2015 / 241682

[0004] Observation using a gel-immersion objective lens has the above-mentioned advantages compared to observation using an immersion objective lens, while having problems specific to gel-immersion objective lenses that do not occur in immersion objective lenses. For example, when the gel is maintained in a state of being adhered to the sample or the sample holder for a long time, the gel is likely to be damaged when separating the gel from the sample or the sample holder. This is an example of such a problem.

[0005] Based on the above situation, an object according to one aspect of the present invention is to provide a technique for suppressing damage to the gel in observation using a gel-immersion objective lens.

[0006] A microscope system according to an aspect of the present invention includes a gel-immersion objective lens with a gel attached to the tip, a stage on which a sample is placed, and a focusing device that changes the distance in the direction of the optical axis between the gel-immersion objective lens and the stage, a microscope including the above, and a control device that controls the microscope. The control device acquires adhesion time information regarding the adhesion time, which is the duration of the adhesion state in which the gel is adhered to the sample or the sample holder that houses the sample, and controls the focusing device so that when the gel-immersion objective lens is retracted before the adhesion time exceeds the predetermined time, the gel-immersion objective lens is retracted at a speed corresponding to the adhesion time.

[0007] According to the above aspect, damage to the gel can be suppressed in observation using a gel-immersion objective lens.

[0008] This is a diagram illustrating the configuration of a microscope system according to one embodiment. This is a diagram illustrating the configuration of a gel immersion objective lens. This is a diagram illustrating a map image. This is a diagram explaining return, contact, and retraction. This is a flowchart illustrating an example of objective lens retraction processing. This is an example of a graph showing the relationship between retraction speed and contact time. This is an example of a table showing the relationship between retraction speed and contact time. This is a flowchart illustrating an example of notification processing. This is a flowchart illustrating an example of forced retraction processing of the objective lens. This is a diagram illustrating an example of automatic control of the focusing device according to user settings. This is a diagram illustrating yet another example of automatic control of the focusing device according to user settings. This is a diagram illustrating yet another example of automatic control of the focusing device according to user settings. This is a diagram illustrating yet another example of automatic control of the focusing device according to user settings. This is a diagram illustrating yet another example of automatic control of the focusing device according to user settings. This is a diagram illustrating the hardware configuration of a computer for realizing a control device.

[0009] Figure 1 is a diagram illustrating the configuration of a microscope system according to one embodiment. Figure 2 is a diagram illustrating the configuration of a gel immersion objective lens. Figure 3 is a diagram illustrating a map image. The microscope system 1 will be described below with reference to Figures 1 to 3.

[0010] The microscope system 1 shown in Figure 1 comprises a microscope 100 having a gel immersion objective lens 130 and a control device 200 for controlling the microscope 100. As shown in Figure 1, the microscope system 1 may also include a plurality of drive controllers (drive controller 301, drive controller 302) that control each motorized part of the microscope 100 according to instructions from the control device 200, and may further include a display device 401, an input device 402, and a jog controller 403 connected to the control device 200.

[0011] The microscope 100 is a magnification observation device that allows observation of an object 10 at a magnified level, and includes a stage 110 on which the object 10 is placed, and a revolving nosepiece 120 to which multiple objective lenses, including a gel immersion objective lens 130, can be attached. The microscope 100 may further include, as shown in Figure 1, a light source unit 140 for transmitted illumination, a light source unit 150 for reflected illumination, an eyepiece 160 for visual observation, and an imaging device 170 for imaging. The imaging device 170 is, for example, a CMOS image sensor or a CCD image sensor, and acquires an image of the sample 11 based on light from the sample 11 (see Figure 2) that constitutes the object 10, which is incident on the sample 11 through the gel immersion objective lens 130.

[0012] The stage 110 and the revolving nosepiece 120 are both motorized units whose operation is controlled by the control device 200. The stage 110 is controlled by the control device 200 via the drive controller 301. The revolving nosepiece 120 is controlled by the control device 200 via the drive controller 302. The light source unit 140, the light source unit 150, and the imaging device 170 may also be controlled by the control device 200, and the control device 200 may perform light emission control and imaging control by controlling these units.

[0013] The microscope system 1 shown in Figure 1 supports both visual observation, where the user looks through the eyepiece 160 to observe the object 10, and imaging, where an image of the object 10 is acquired by the imaging device 170. The image of the object 10 acquired by the imaging device 170 is output to the control device 200. The control device 200 displays the image of the object 10 acquired by the imaging device 170 on the display device 401, so the user can observe the object 10 on the display device 401. Alternatively, the user can directly observe the object 10 by looking through the eyepiece 160.

[0014] The object to be observed 10, placed on the stage 110, includes a sample 11 and a sample holder 12 that contains the sample 11, as shown in Figure 2. The sample 11 is not particularly limited, but could be, for example, cultured cells. The sample holder 12 is not particularly limited, but could be, for example, a glass-bottom dish. The stage 110 is an electrically powered stage that moves in the XY direction perpendicular to the optical axis of the objective lens used for observation. The control device 200 controls the rotation of the motor 181 of the stage 110 via the drive controller 301 to move the stage 110 in the XY direction. This changes the position of the sample 11 relative to the objective lens in the XY direction, thereby moving the field of view of the microscope 100.

[0015] The revolving nosepiece 120 is an electric revolving nosepiece with multiple mounting holes for attaching multiple objective lenses. The revolving nosepiece 120 is a switching unit that switches the objective lens used for observation, and by rotating around its axis, it switches the objective lens positioned on the observation optical path from among the multiple objective lenses attached to the multiple mounting holes. The control device 200 controls the rotation of the motor 182 of the revolving nosepiece 120 via the drive controller 302 to rotate the revolving nosepiece 120. This changes the observation magnification of the microscope 100 by inserting the objective lens to be used for observation into the optical path.

[0016] Furthermore, the revolving nosepiece 120 also functions as a focusing device, changing the distance in the direction of the optical axis between the position of the objective lens used for observation and the stage 110. The control device 200 controls the rotation of the motor 183 of the revolving nosepiece 120 via the drive controller 302, thereby moving the revolving nosepiece 120 in the Z direction. This changes the position of the sample 11 relative to the position of the objective lens in the Z direction, thereby moving the focus position of the microscope 100. Alternatively, the stage 110 may function as a focusing device instead of the revolving nosepiece 120. The distance in the direction of the optical axis between the position of the objective lens used for observation and the stage 110 may be changed by moving the stage 110 in the Z direction instead of the revolving nosepiece 120.

[0017] The revolving nosepiece 120 is equipped with multiple objective lenses, including a gel immersion objective lens 130. As shown in Figure 2, the gel immersion objective lens 130 is an objective lens in which a gel 134 is attached to the tip 131a of the objective lens body 131, and is used for observation with the gel 134 in contact with the object to be observed 10. More specifically, the gel immersion objective lens 130 includes an objective lens body 131 and an attachment 132 attached to the tip 131a of the objective lens body 131. The attachment 132 further includes a frame 133 fixed to the tip 131a and a gel 134 held by the frame 133. The gel immersion objective lens 130 is configured such that the attachment 132 is attached to the tip 131a, so that the gel 134 is in gapless contact with the tip lens 131b exposed from the tip 131a. In this example, the microscope 100 is an inverted microscope, and observation is performed with the gel 134 of the gel immersion objective lens 130 in contact with the bottom surface of the sample holder 12. The attachment 132 of the gel immersion objective lens 130 is detachable, and if the gel 134 deteriorates, the gel 134 can be replaced by removing and replacing the attachment 132.

[0018] The control device 200 is, for example, a computer including a processor and memory. The control device 200 controls the operation of the microscope 100 by having the processor execute a program of control software 210 stored in memory. The user of the microscope system 1 may input commands to the control device 200 by operating the input device 402 or Jog controller 403 while viewing the application screen displayed on the display device 401, and the control device 200 may control the microscope 100 according to the commands input by the user.

[0019] The microscope system 1 also has a function to display a map image 501. The map image 501 is displayed in a window 500 of an application screen displayed on the display device 401, for example, as shown in Figure 3. A bounding box C indicating the current field of view may be displayed on the map image 501. The map image is an image of the object being observed 10, which is an image that captures a wider area than the field of view of the microscope 100. For example, the map image is an image that captures a wide area of ​​the object being observed 10 using an objective lens with a lower magnification than the objective lens used for observation. The map image may also be a composite image created by stitching together multiple images.

[0020] The microscope system 1 further has the function of executing various imaging processes according to user settings. The imaging process is an automated process performed by the control device 200 controlling the microscope 100, and includes imaging (image acquisition) by the imaging device 170. Examples of imaging processes include stitched imaging, multi-point imaging, Z-stack imaging, and time-lapse imaging. Here, stitched imaging is an imaging process in which a wide area specified by the user is continuously photographed in multiple sections, and the obtained images are stitched together to acquire a single image. An image created by stitching together multiple images in stitched imaging is called a stitched image. Multi-point imaging is an imaging process in which multiple positions on a sample specified by the user are continuously photographed while the stage is automatically moved. Z-stack imaging is an imaging process in which a range of Z positions (positions in the optical axis direction of the gel immersion objective lens 130) specified by the user is continuously photographed at intervals specified by the user while the focusing device is automatically moved. Time-lapse imaging is a process in which any imaging process is repeatedly executed at time intervals specified by the user. Furthermore, time-lapse photography can be considered as a single shooting process (broad sense) encompassing multiple shooting processes (narrow sense).

[0021] In the microscope system 1 configured as described above, when observation is performed using a gel immersion objective lens, a control specific to the gel immersion objective lens is performed, which differs from the control performed when observation is performed using a dry objective lens or a liquid immersion objective lens. The control specific to the gel immersion objective lens will be described below.

[0022] Figure 4 illustrates the return, contact, and retraction processes. Observation using the gel immersion objective lens 130 is performed in a contact state, as shown in Figure 4, with the gel immersion objective lens 130 positioned at the observation position Z2 and the gel 134 in close contact with the object to be observed 10. The process of bringing the gel immersion objective lens 130 closer to the object to be observed 10 to create this contact state is called the return process, and the process of moving the gel immersion objective lens 130 away from the object to be observed 10 to release this contact state is called the retraction process. Note that the contact state is not simply a state in which the gel 134 and the object to be observed 10 are in contact, but a state in which the gel 134 and the object to be observed 10 are in contact AND the gel immersion objective lens 130 is positioned at the observation position Z2 by the focusing device. In other words, the contact state is a state in which the gel 134 and the object to be observed are in contact AND a force is applied in the direction that brings the gel immersion objective lens 130 closer to the object to be observed, resulting in the gel 134 being compressed. On the other hand, the contact state simply refers to a state in which the gel 134 and the object being observed are not separated.

[0023] If the contact state continues, the gel 134 becomes difficult to peel off from the object to be observed 10. Due to this property of the gel 134, as shown in Figure 4, even if the gel immersion objective lens 130 is retracted to the contact position Z1 where the gel 134 and the object to be observed 10 began to come into contact during the recovery process, the gel 134 does not separate from the object to be observed 10, and tensile stress acts on the gel 134. If the gel immersion objective lens 130 is retracted from the contact position Z1 to the retracted position Z0 while the gel 134 is still attached to the object to be observed 10 and tensile stress is still applied to the gel 134, the gel 134 may be damaged during that time. In particularly severe cases, as shown in Figure 4, the gel 134 may tear.

[0024] The inventors of this invention have diligently researched and discovered that the resistance of the gel 134 to peeling off, that is, the high adhesion of the gel 134, increases as the adhesion continues, that is, as the adhesion time, which is the duration of the adhesion state in which the gel 134 is in close contact with the object to be observed 10, increases. Furthermore, through numerous experiments, they have found that damage to the gel 134 can be avoided by suppressing the speed at which the gel immersion objective lens 130 is retracted (hereinafter referred to as the retraction speed) when the adhesion time is relatively short, but that when the adhesion time is long, it becomes difficult to avoid damage to the gel 134 by simply suppressing the retraction speed.

[0025] Based on these points, the microscope system 1 is configured such that the control device 200 performs two specific controls to suppress damage to the gel 134 during the retraction process of the gel immersion objective lens 130: (1) a control that retracts the gel immersion objective lens 130 at a speed corresponding to the contact time, and (2) a control that retracts the gel immersion objective lens 130 by repeatedly moving and stopping. More specifically, at the start of the retraction process, the control device 200 determines whether the contact time exceeds the allowable contact time. If it determines that it does not exceed the allowable contact time, it executes control (1); if it determines that it exceeds the allowable contact time, it executes control (2).

[0026] The allowable contact time is the maximum contact time beyond which damage to the gel 134 cannot be avoided simply by reducing the retraction speed. In other words, the allowable contact time is the maximum contact time beyond which the gel 134 can be peeled off without damage when the retraction speed is reduced to a predetermined minimum speed. The predetermined minimum speed is, for example, a speed close to 0, but is not limited to this. The minimum speed can be, for example, a speed slower than the normal retraction speed when using a dry-type objective lens, and may be set arbitrarily by the user.

[0027] Furthermore, the contact time used for the determination is measured by the control device 200. The control device 200 may be pre-configured to measure the contact time using, for example, a combination of a built-in hardware timer and a software implementation. The control device 200 may, during the recovery process, determine the start of contact between the gel 134 and the object to be observed 10 based on the Z position of the gel immersion objective lens 130 and start measuring the contact time, or it may acquire the contact time measured at the start of the retraction process and perform the determination described above.

[0028] Figure 5 is a flowchart showing an example of the objective lens retraction process. Figure 6 is an example of a graph showing the relationship between retraction speed and contact time. Figure 7 is an example of a table showing the relationship between retraction speed and contact time. Hereafter, referring to Figures 5 to 7, the objective lens retraction process will be described as a specific example of the unique control performed during observation using gel immersion objective lenses. The objective lens retraction process described below is an example of control specific to gel immersion objective lenses, performed to suppress damage to the gel.

[0029] When the objective lens retraction process is initiated in accordance with user instructions or as an operation during a pre-set shooting process, as shown in Figure 5, the control device 200 first acquires the contact time and the allowable contact time (step S1). Here, the contact time being measured by the control device 200 and the allowable contact time pre-stored in the control device 200 are acquired. The allowable contact time may be pre-stored for each gel immersion objective lens, for example, and in step S1, the control device 200 only needs to acquire the allowable contact time corresponding to the gel immersion objective lens being used (in this case, the gel immersion objective lens 130).

[0030] After obtaining the contact time and the allowable contact time, the control device 200 determines whether the contact time exceeds the allowable contact time (step S2). If it determines that the contact time does not exceed the allowable contact time (step S2NO), the control device 200 controls the focusing device to retract the gel immersion objective lens 130 at a speed corresponding to the contact time obtained in step S1 (step S3), and ends the retraction process.

[0031] In step S3, the control device 200 first determines the retraction speed according to the contact time. The control device 200 stores the relationship between the contact time and the retraction speed at which the gel is not damaged, which has been determined in advance through simulations or experiments. The retraction speed according to the contact time can be determined based on the contact time using this relationship. The relationship between the contact time and the retraction speed at which the gel is not damaged can be stored in any format. This relationship may be stored as a graphable function equation F as shown in Figure 6, or in a table T as shown in Figure 7. As shown in Figures 6 and 7, the contact time and the retraction speed are negatively correlated.

[0032] Furthermore, the adhesion of the gel 134 may vary depending on various usage conditions other than the adhesion time (hereinafter referred to as gel usage conditions). Taking this into consideration, the control device 200 may determine the retraction speed based on the adhesion time and the gel usage conditions. For example, multiple relationships associated with the gel usage conditions (relationship between adhesion time and retraction speed) may be stored in advance in the control device 200, and the control device 200 may determine one relationship from among the multiple relationships stored in advance based on the gel usage conditions, and then determine the retraction speed based on the adhesion time from the determined relationship.

[0033] The gel usage conditions described above preferably include at least one of the following: the specifications of the gel 134 (e.g., shape, size, material, consistency, etc.), the degree of degradation of the gel 134 (e.g., cumulative number of contacts, cumulative contact time, etc.), the environment in which the gel 134 is placed (e.g., temperature around the gel 134, type of sample holder to which the gel 134 is in contact (glass, plastic, presence or absence of coating, etc.)), and the force applied to the gel 134 (Z position of the gel immersion objective lens 130 in the contact state (observation position), working distance of the gel immersion objective lens, etc.). These gel usage conditions may be specified by user input or specified without user input. For example, the force applied to the gel 134 may be specified based on the position information of the focusing device. The cumulative number of contacts and cumulative contact time of the gel 134 may be configured to be recorded in advance by software. The temperature around the gel 134 may be measured by a temperature sensor.

[0034] In step S3, once the retraction speed corresponding to the contact state is determined, the control device 200 controls the focusing device to retract the gel immersion objective lens 130 at the determined retraction speed. More specifically, the control device 200 controls the focusing device to retract the gel immersion objective lens 130 to the retraction position Z0 at a determined constant retraction speed.

[0035] This prevents the gel 134 from being damaged during the retraction process due to the retraction speed of the gel immersion objective lens 130 being too fast. Furthermore, since an appropriate retraction speed is set according to the contact time, it is possible to prevent situations where the retraction speed is set excessively slowly out of fear of damaging the gel 134, resulting in a lengthy retraction process.

[0036] On the other hand, if the control device 200 determines in step S2 that the contact time exceeds the allowable contact time (step S2 YES), it controls the focusing device to repeatedly move and stop the gel immersion objective lens 130 (steps S4 to S6).

[0037] More specifically, the control device 200 first controls the focusing device to retract the gel immersion objective lens 130 at a low speed by a predetermined distance (step S4). In other words, the control device 200 retracts the gel immersion objective lens 130 by a predetermined distance, and then stops the movement of the gel immersion objective lens 130. The predetermined distance is a distance that is sufficiently shorter than the distance between the observation position Z2 and the retraction position Z0, for example, one-tenth or one-hundredth of the distance between the observation position Z2 and the contact position Z1. The low speed is a speed slower than the normal retraction speed when using a dry objective lens. For example, it may be a speed slower than the retraction speed corresponding to a very short contact time (for example, 3000 μm / s in Figure 7), or it may be a speed faster than the retraction speed corresponding to the allowable contact time.

[0038] Once the gel immersion objective lens 130 has retracted by a predetermined distance, the control device 200 determines whether the gel immersion objective lens 130 has reached the retracted position Z0 (step S5). If the control device 200 determines that the gel immersion objective lens 130 has not reached the retracted position Z0 (step S5NO), it waits for a certain period of time with the gel immersion objective lens 130 stopped (step S6). The certain period of time is not particularly limited, but it is desirable that it be sufficient time for the force that causes the gel 134 to peel off the object of observation 10, generated by the retraction of the gel immersion objective lens 130 by a predetermined distance, to be firmly transmitted to the boundary between the gel 134 and the object of observation 10, and for the state of the gel 134 to stabilize thereafter. Therefore, the certain period of time should be longer than the time it takes for the deformation of the gel 134 to stop, that is, longer than the time it takes for the area of ​​gel adhering to the container to become constant. Note that the time it takes for the deformation of the gel 134 to stop may vary depending on the properties of the gel 134, temperature, etc., so the certain period of time may be appropriately adjusted by the settings of the microscope system 1.

[0039] After waiting for a certain period of time in step S6, the control device 200 executes the process in step S4 again. The control device 200 repeatedly executes the processes from step S4 to step S6 until it determines in step S5 that the gel immersion objective lens 130 has reached the retracted position Z0.

[0040] Instead of retracting the gel immersion objective lens 130 to the retraction position Z0 all at once, by repeatedly moving and stopping it in small increments, the gel immersion objective lens 130 can be retracted while suppressing damage to the gel 134, even if the gel 134 is in close contact with the object being observed 10 for longer than the allowable contact time.

[0041] As described above, by performing the retraction process shown in Figure 5, the microscope system 1 can retract the gel immersion objective lens 130 while suppressing damage to the gel 134, regardless of the contact time of the gel immersion objective lens 130.

[0042] FIG. 8 is a flowchart showing an example of notification processing. FIG. 9 is a flowchart showing an example of forced retraction processing of the objective lens. As a specific example of unique control performed in observation using a gel-immersed objective lens, FIGS. 5 to 7 exemplify control capable of suppressing gel damage regardless of the contact time. However, the control device 200 may execute control for suppressing gel damage by suppressing excessive prolongation of the contact time, such as the notification processing shown in FIG. 8 or the forced retraction processing shown in FIG. 9. These controls are particularly suitable when applied to manual shooting.

[0043] The notification processing shown in FIG. 8 is a process of performing a notification prompting retraction of the gel-immersed objective lens 130 based on the contact time, and is started, for example, when the gel-immersed objective lens 130 is inserted into the observation optical path. When starting the notification processing shown in FIG. 8, the control device 200 first acquires a reference time (step S11). Here, the reference time stored in the control device 200 in advance is acquired. The reference time may be stored in advance for each gel-immersed objective lens, for example, and the control device 200 may acquire the reference time corresponding to the gel-immersed objective lens in use (in this case, the gel-immersed objective lens 130) in step S11.

[0044] The reference time is not particularly limited, but it is desirable that it be less than or equal to the contact allowable time. The reference time may be the same as the contact allowable time. It is more desirable that the reference time be a time sufficiently short with respect to the contact allowable time so that the user's operation in response to the processing of step S15 described later allows the gel-immersed objective lens 130 to be retracted before the contact time exceeds the contact allowable time.

[0045] After acquiring the reference time, the control device 200 determines whether the gel-immersed objective lens 130 is in a contact state (step S12). In step S12, the control device 200 may determine whether it is in a contact state based on, for example, the Z position of the gel-immersed objective lens 130. Thereafter, when the control device 200 determines that it is in a contact state (step S12 YES), it acquires the contact time (step S13). In step S13, the contact time being measured by the control device 200 is acquired.

[0046] When the contact time is obtained, the control device 200 determines whether the contact time exceeds the reference time (step S14). If it is determined that the contact time does not exceed the reference time (step S14 NO), the control device 200 repeats the processes from step S12 to step S14. On the other hand, if it is determined that the contact time exceeds the reference time (step S14 YES), the control device 200 issues a notice prompting evacuation (step S15) and ends the notification process. The notice prompting evacuation is performed, for example, by displaying information prompting evacuation on the display device 401. However, in step S15, the control device 200 may prompt the user to evacuate the gel immersion objective lens 130 using sound, light, or the like.

[0047] By performing the notification process shown in FIG. 8, the microscope system 1 can prompt the user to evacuate the gel immersion objective lens 130 before the contact time becomes long and the gel 134 is likely to be damaged. As a result, the user can recognize the need for evacuation during the observation operation, so the user can voluntarily evacuate the gel immersion objective lens 130 early. In addition, since the user can select the timing to evacuate the gel immersion objective lens 130 by himself / herself, the user can select a good timing for the work break or the like and evacuate the gel immersion objective lens 130. Therefore, the decrease in the observation efficiency associated with the evacuation of the gel immersion objective lens 130 can be minimized. When evacuating the gel immersion objective lens 130, it is desirable to evacuate at an evacuation speed corresponding to the contact time.

[0048] The forced evacuation process shown in FIG. 9 is a process of controlling the focusing device so as to forcibly evacuate the gel immersion objective lens 130 based on the contact time. For example, it is started when the gel immersion objective lens 130 is inserted into the observation optical path. The processes from step S21 to step S24 of the forced evacuation process shown in FIG. 9 are the same as the processes from step S11 to step S14 of the notification process shown in FIG. 8.

[0049] In step S24, if the control device 200 determines that the contact time does not exceed the reference time (step S24 NO), it repeats the process from step S22 to step S24. On the other hand, if it determines that the contact time exceeds the reference time (step S24 YES), the control device 200 controls the focusing device to forcibly retract the gel immersion objective lens 130 (step S25), and terminates the forced retraction process. In step S25, it is desirable for the control device 200 to retract the gel immersion objective lens 130 at a retraction speed corresponding to the contact time, similar to step S3 in Figure 5. Alternatively, in step S25, the control device 200 may retract the gel immersion objective lens 130 by repeatedly moving and stopping in small increments, as shown in steps S4 to S8 in Figure 5. Whether to retract at a constant speed or in small increments may be determined, for example, based on the contact time.

[0050] By performing the forced retraction procedure shown in Figure 9, the microscope system 1 can forcibly retract the gel immersion objective lens 130 before the contact time becomes prolonged and the gel 134 becomes susceptible to damage. This significantly reduces the risk of damage to the gel 134.

[0051] The above description primarily focuses on the control specific to the gel immersion objective lens 130, assuming a user freely observing the object 10. However, the retraction process illustrated in Figure 5 above may also be applied to retraction processes during imaging processes (e.g., multi-point imaging, composite imaging, etc.) performed by controlling the microscope 100.

[0052] Furthermore, the retraction process illustrated in Figure 5 may be automatically executed after the completion of the imaging process, which is performed according to user settings. For example, if setting C1 shown in Figure 10 is specified by the user, the setting may be changed so that the retraction process shown in Figure 5 is executed after the imaging process, and the control device 200 may control the microscope 100 according to the changed setting E1. That is, the control device 200 may execute the imaging process and, after the completion of the imaging process, control the focusing device to retract the gel immersion objective lens at a speed corresponding to the contact time during the imaging process. At this time, it may also be determined whether or not the contact time exceeds the allowable contact time. If the control device 200 determines that the contact time during the imaging process does not exceed the allowable contact time, it may control the focusing device to retract the gel immersion objective lens at a speed corresponding to the contact time during the imaging process after the completion of the imaging process. If the control device 200 determines that the contact time during the imaging process exceeds the allowable contact time, it may control the focusing device to repeatedly move and stop the gel immersion objective lens 130 in small increments after the completion of the imaging process.

[0053] For example, as shown in Figures 11 to 14, when time-lapse photography is specified by the user, the settings may be changed so that the retraction process shown in Figure 5 is executed after each shooting process that constitutes the time-lapse photography, and the control device 200 may control the microscope 100 according to the changed settings.

[0054] If the waiting time between scheduled shooting processes in time-lapse photography is longer than the time required for the gel immersion objective lens 130 to retract and return, the control device 200 may change the user-specified setting C2, as shown in Figure 11, so that the retraction process shown in Figure 5 is performed after each shooting process, and may control the microscope 100 according to the changed setting E2. More specifically, the focusing device may be controlled to retract the gel immersion objective lens 130 at a speed corresponding to the contact time during the shooting process after the completion of each scheduled shooting process in time-lapse photography, and the focusing device may be controlled to return the gel immersion objective lens 130 before the start of each shooting process. Furthermore, if the contact time exceeds the allowable contact time, the control device 200 may control the focusing device to repeatedly move and stop the gel immersion objective lens 130 in small increments after the completion of each shooting process, and may control the focusing device to return the gel immersion objective lens 130 before the start of each shooting process. Furthermore, it is desirable that the control device 200 adjusts the timing of initiating the recovery process so that the shooting process can be started at the scheduled time by estimating the time required for recovery in advance.

[0055] Furthermore, if the waiting time between scheduled shooting processes in time-lapse photography is shorter than the time required for the gel immersion objective lens 130 to retract and return, the control device 200 may postpone the scheduled start time of the shooting process following the shorter waiting time, or shorten the time of the shooting process preceding the shorter waiting time. That is, as shown in Figure 12, the control device 200 may change the user-specified setting C3 to setting E3 and control the microscope 100 according to setting E3, or as shown in Figure 13, it may change the user-specified setting C4 to setting E4 and control the microscope 100 according to setting E4. The method for shortening the shooting process time is not particularly limited, but for example, the shooting process time can be shortened by shortening the number of shots taken, the exposure time, etc. in each shooting process.

[0056] Furthermore, if the waiting time between scheduled shooting processes in time-lapse photography is shorter than the time required for the gel immersion objective lens 130 to retract and return, the control device 200 may change its settings so that the retraction process shown in Figure 5 is executed after the last shooting process of the scheduled shooting processes in time-lapse photography, rather than changing the settings so that the retraction process shown in Figure 5 is executed after each shooting process constituting the time-lapse photography. In other words, as shown in Figure 14, the user may change the setting C5 to execute the retraction process shown in Figure 5 after the last shooting process, and the microscope 100 may be controlled according to the changed setting E5. More specifically, in the retraction process performed after the last shooting process, the control device 200 may control the focusing device so that the gel immersion objective lens 130 is retracted at a speed corresponding to the contact time during time-lapse photography. Also, if the contact time during time-lapse photography exceeds the allowable contact time, the control device 200 may control the focusing device so that the gel immersion objective lens 130 is moved and stopped repeatedly in small increments after the last shooting process.

[0057] As described above, by automatically performing a retraction process after the shooting process, it is possible to prevent the gel immersion objective lens 130 from being left in a tight-fitting state for a long period of time, thereby suppressing damage to the gel.

[0058] Figure 15 is a diagram illustrating the hardware configuration of a computer 200a for realizing the control device 200 according to the above-described embodiment. The hardware configuration shown in Figure 15 includes, for example, a processor 201, memory 202, storage device 203, reader 204, communication interface 206, and input / output interface 207. The processor 201, memory 202, storage device 203, reader 204, communication interface 206, and input / output interface 207 are connected to each other, for example, via a bus 208.

[0059] The processor 201 executes the control processes illustrated in Figures 5, 8, and 9 by reading the program stored in the storage device 203 into the memory 202 and executing it. The memory 202 is, for example, a semiconductor memory. The storage device 203 is, for example, a semiconductor memory such as a hard disk or flash memory, or an external storage device.

[0060] The reader 204 accesses the removable storage medium 205, for example, according to instructions from the processor 201. The removable storage medium 205 is implemented by, for example, a semiconductor device, a medium through which information is input / output by magnetic action, or a medium through which information is input / output by optical action. The communication interface 206 communicates with other devices, for example, according to instructions from the processor 201. The input / output interface 207 is, for example, an interface between the display device 401, the input device 402, the Jog controller 403, the drive controller 301, and the drive controller 302.

[0061] The programs executed by the processor 201 are provided to the computer in the following forms, for example: (1) pre-installed in the storage device 203; (2) provided via a removable storage medium 205; (3) provided from a server such as a program server.

[0062] Note that the computer hardware configuration for realizing the control device described with reference to Figure 15 is illustrative, and the embodiment is not limited thereto. For example, some of the above configurations may be deleted, or new configurations may be added. In another embodiment, for example, some or all of the functions of the above control device may be implemented as hardware such as FPGA (Field Programmable Gate Array), SoC (System-on-a-Chip), ASIC (Application Specific Integrated Circuit), and PLD (Programmable Logic Device).

[0063] The embodiments described above are provided as concrete examples to facilitate understanding of the invention, and the present invention is not limited to the embodiments described above, but should be understood as encompassing various modifications and alternative forms of the embodiments described above. For example, it will be understood that the embodiments described above can be materialized by modifying the components without departing from the spirit thereof. It will also be understood that various embodiments can be implemented by appropriately combining the multiple components disclosed in the embodiments described above. Furthermore, it will be understood by those skilled in the art that various embodiments can be implemented by deleting some components from all the components shown in the embodiments, or by adding some components to the components shown in the embodiments.

[0064] The above-described embodiment shows an example of determining whether the contact time exceeds the allowable contact time, but the determination process may be omitted. For example, depending on the set shooting process, it may be possible to predict whether the contact time will exceed the allowable contact time during that shooting process. In such cases, the control to be performed after the shooting process may be determined depending on the type of shooting process. After a shooting process in which it is expected that the contact time will not exceed the allowable contact time, the retraction process may be performed at a retraction speed corresponding to the contact time without determining whether or not the contact time exceeds the allowable contact time. Alternatively, after a shooting process in which it is expected that the contact time will exceed the allowable contact time, the gel immersion objective lens 130 may be retracted while repeatedly making slight movements and stopping, without determining whether or not the contact time exceeds the allowable contact time.

[0065] The above-described embodiment shows an example of obtaining information by measuring the contact time, but the control device does not necessarily have to measure the contact time; it only needs to obtain contact time information. The contact time information may be the measured contact time, the contact time stored in advance in a storage device, or the contact time calculated based on a set value. For example, if a predetermined shooting process is to be executed, the contact time corresponding to that shooting process may be stored in advance as contact time information in a storage device, and the control device may obtain this contact time information by reading it from the storage device. Alternatively, if a set shooting process is to be executed, the control device may calculate the contact time based on the set value using a predetermined calculation and obtain it as contact time information.

[0066] This application is based on Japanese Patent Application No. 2024-196614, filed on November 11, 2024. All of its contents are included herein.

[0067] 1: Microscope system, 10: Object to be observed, 11: Sample, 12: Sample holder, 100: Microscope, 110: Stage, 120: Revolving nosepiece, 130: Gel immersion objective lens, 131: Objective lens body, 131a: Tip, 131b: Tip lens, 132: Attachment, 133: Frame, 134: Gel, 140, 150: Light source unit, 160: Eyepiece, 170: Imaging device, 181, 182, 183: Motor, 200: Control device, 200a: Computer, 201: Processor, 202 : Memory, 203: Storage device, 204: Reader, 205: Removable storage medium, 206: Communication interface, 207: Input / output interface, 208: Bus, 210: Control software, 301, 302: Drive controller, 401: Display device, 402: Input device, 403: Jog controller, 500: Window, 501: Map image, C: Bounding box, C1-C5, E1-E5: Settings, F: Function expression, T: Table, Z0: Retracted position, Z1: Contact position, Z2: Observation position

Claims

1. A microscope comprising: a gel immersion objective lens with a gel attached to its tip; a stage on which a sample is placed; a focusing device for changing the distance in the direction of the optical axis between the gel immersion objective lens and the stage; and a control device for controlling the microscope, wherein the control device acquires contact time information relating to the contact time, which is the duration of the contact state in which the gel is in close contact with the sample or a sample holder containing the sample; and controls the focusing device to retract the gel immersion objective lens at a speed corresponding to the contact time when the gel immersion objective lens is to be retracted before the contact time exceeds a predetermined time.

2. The microscope system according to claim 1, wherein the control device controls the focusing device so as to repeatedly move and stop the gel immersion objective lens when the gel immersion objective lens is retracted after the contact time exceeds the predetermined time.

3. A microscope system according to claim 1, characterized in that the contact time and the retraction speed for retracting the gel immersion objective lens are in a negative correlation.

4. The microscope system according to claim 1, wherein the control device provides a notification prompting the retraction of the gel immersion objective lens based on the contact time.

5. A microscope system according to claim 1, wherein the microscope comprises an imaging device for acquiring an image of the sample, the control device controls the microscope to perform a shooting process including image acquisition by the imaging device, and after the completion of the shooting process, determines whether the contact time during the shooting process exceeds a predetermined time, and controls the focusing device to retract the gel immersion objective lens at a speed corresponding to the contact time if it is determined that the contact time does not exceed the predetermined time.

6. The microscope system according to claim 5, wherein the control device controls the microscope to perform time-lapse photography, determines whether the contact time during the photography process exceeds the predetermined time after the completion of each scheduled photography process in the time-lapse photography, and controls the focusing device to retract the gel immersion objective lens at a speed corresponding to the contact time if it is determined that the contact time does not exceed the predetermined time.

7. The microscope system according to claim 6, wherein the control device postpones the scheduled start time of the imaging process following the waiting time when the waiting time between scheduled imaging processes in the time-lapse imaging is shorter than the time required for the gel immersion objective lens to retract and return.

8. The microscope system according to claim 6, wherein the control device shortens the time of the imaging process preceding the waiting time when the waiting time between scheduled imaging processes in the time-lapse imaging is shorter than the time required for the retraction and return of the gel immersion objective lens.

9. A microscope system according to claim 1, wherein the microscope comprises an imaging device for acquiring an image of the sample, and the control device controls the focusing device such that, when the waiting time between scheduled shooting processes in time-lapse photography performed by controlling the microscope is shorter than the time required for the retraction and return of the gel immersion objective lens, the gel immersion objective lens is retracted at a speed corresponding to the contact time during time-lapse photography after the completion of the last shooting process among the scheduled shooting processes in time-lapse photography.

10. A microscope system according to claim 1, wherein the control device controls the focusing device to forcibly retract the gel immersion objective lens based on the contact time.

11. The microscope system according to claim 1, wherein the control device determines the retraction speed for retracting the gel immersion objective lens according to the contact time and at least one of the following: the consistency of the gel, the shape of the gel, the temperature around the gel, the position of the gel in the contact state, the type of sample holder, the cumulative number of contacts of the gel, and the cumulative contact time of the gel.

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