JP5018253B2 - Electric microscope - Google Patents

Description

  The present invention relates to an electric microscope that controls operation of a plurality of electric devices using control information input from the outside.

  Microscopes are used for magnifying and observing minute samples (specimens), recording observation images as photographs and video images, and being used in a wide range of fields from biological to industrial inspection processes. (Patent Document 1 etc.).

  Such a microscope is connected to an input device such as a PC (Personal Computer), and the operation of each part of the microscope is controlled based on an input operation of the input device. In the case of such a microscope, since input operations are performed for each control, it takes a very long time to obtain an observation image or video image of a sample under one imaging condition. When recording an observation image of a sample such as a biological tissue or a biological cell under a plurality of imaging conditions, there is a problem that if the observation time under one imaging condition becomes long, the biological tissue or the biological cell is weakened unnecessarily. .

In order to shorten the time until the observation image or video image of the sample is acquired, for example, the operation of each part of the microscope is accelerated, the time from the input operation of the input device to the control of each part of the microscope, that is, For example, the communication time between the input device and the microscope can be shortened, or the control order or the like in each part of the microscope can be set in advance to reduce the input operation in the input device.
JP 2006-011149 A

  However, since a microscope has many optical components and electric mechanisms, the input operation is complicated. Even if the operation of each part of the microscope is accelerated or the communication time is shortened, one imaging condition It is not effective as a method for shortening the imaging time below. In addition, it is considered effective to set the control order in each part of the microscope in advance and reduce input operations in the input device, but the control order set by the input device is managed on the input device side. Therefore, every time necessary control is executed, a corresponding control start signal is transmitted from the input device to the microscope. For this reason, it is hard to say that the imaging time under one imaging condition can be effectively shortened by simply setting the control order in advance.

  The present invention has been invented to solve the above-described problems, and is an electric motor capable of efficiently shortening the control time when controlling each part of the microscope in accordance with the control sequence set by the input device. An object is to provide a microscope.

In order to solve the above-described problems, an electric microscope according to the present invention includes an imaging device that performs imaging of a specimen, a plurality of electric devices that operate as imaging preparations of the specimen by the imaging device, the imaging device, and the plurality of imaging devices. A storage unit that stores control information for the electric device, a control unit that reads the control information stored in the storage unit, and controls the imaging device and the plurality of electric devices based on the read control information; And when the control information read from the storage unit includes control information for simultaneously performing a plurality of operation controls, the control unit simultaneously operates a target electric device among the plurality of electric devices. And the control information read from the storage unit includes control information for continuously performing a plurality of operation controls. Interlocking control for continuously operating the electric device to be set, and the control information read from the storage unit sets a waiting time from the start of the simultaneous control to the start of the interlocking control, and the waiting time has elapsed The control unit determines whether or not the standby time is set on the condition that the control of any of the control contents executed in the simultaneous control is completed from the start of the simultaneous control. And standby control for determining whether or not the standby time has elapsed .

Also, to allow the input of an imaging condition, an external input device for generating the control information based on the inputted image pickup condition is connected, the storage unit, the control information generated by the external input device It is memorized.

Further, the control information includes position information set based on the imaging conditions in addition to control codes provided corresponding to the imaging device and the plurality of electric devices.

  According to the present invention, when operation control of a plurality of electric devices is performed, the next operation control is not performed unless one of the operation controls is finished. According to this, it is possible to shorten the preparation period until the specimen is imaged in the imaging apparatus.

As shown in FIG. 1, the microscope 10 is connected to an external input device 75 such as a PC (Personal Computer). By operating the external input device 75, each part of the microscope 10 is controlled, and Obtain observations and specimen images.
The observation method of the microscope 10 includes fluorescence observation in which the specimen 18 is observed using excitation light from the excitation light source 11 and transmission observation in which the specimen 18 is observed using illumination light from the light source 30. .
The excitation light source 11 is used when the specimen 18 is observed using the excitation light or when the specimen image is captured. The excitation light source 11 emits excitation light having a short wavelength (for example, 400 nm). The excitation light emitted from the excitation light source 11 reaches the dichroic mirror 16 via the collector lens 12, the shutter 13, and the excitation filter 14. The excitation light is reflected by the dichroic mirror 16 and then incident on the specimen 18 on the stage 38 through the objective lens 17 and the like.

  The excitation filter 14 is provided to extract light having a wavelength necessary for excitation of the sample 18 from the excitation light source 11. As the excitation filter 14, a plurality of filters having different wavelength ranges of light to be transmitted are prepared, and filters according to the wavelength to be extracted are arranged on the optical path.

  The specimen 18 placed on the stage 38 is stained with a fluorescent reagent, and fluorescence is generated from the stained portion by irradiation with this excitation light. This fluorescence becomes light having a longer wavelength (for example, 500 nm) than the excitation light. The fluorescence in this wavelength band is collected by the objective lens 17 and then transmitted through the fluorescence filter 19 and the dichroic mirror 16.

  The fluorescence filter 19 is provided for extracting fluorescence emitted from the specimen 18. As the fluorescent filter 19, a plurality of filters having different wavelength ranges of light to be transmitted are prepared, and filters according to the wavelength range of the fluorescence to be extracted are arranged on the optical path.

  The fluorescence transmitted through the dichroic mirror 16 reaches the optical path dividing prism 22 through the absorption filter 20 and the imaging lens 21.

  The absorption filter 20 separates scattered light and the like generated when the fluorescence passes through the dichroic mirror 16 from the fluorescence. The absorption filter 20 is also provided with a plurality of filters having different wavelength ranges of light to be transmitted, and any one of these filters is disposed on the optical path.

  The optical path splitting prism 22 reflects part of the fluorescence and supplies it to the eyepiece lens 24. The user (observer) can directly observe the fluorescent image through the eyepiece 24. On the other hand, the remaining fluorescence passes through the optical path splitting prism 22 and then enters the imaging device 26. A fluorescence image is acquired when fluorescence enters the imaging device 26. The operation of the image pickup device 26 is controlled by an image pickup control circuit 49.

  On the other hand, when performing transmission observation, the light source 30 is used. The light source 30 emits illumination light of, for example, 800 nm, which is less damaging to the biological specimen than the excitation light. This illumination light reaches the total reflection mirror 33 via the collector lens 31 and the shutter 32. The illumination light is reflected by the total reflection mirror 33, is limited to a specific wavelength via the band pass filter 34, and then enters the polarizer 35. The linearly polarized light emitted from the polarizer 35 passes through a Wollaston prism (birefringent element) 36 and is divided into two orthogonal linearly polarized lights. The two linearly polarized lights are collected by the condenser lens 37 and irradiated on the back side of the specimen 18 on the stage 38. When these two linearly polarized lights are transmitted through the sample 18, an inherent phase difference (shear amount) is generated.

  The transmitted light (two linearly polarized lights here) that has passed through the specimen 18 in this way is collected by the objective lens 17 and then reaches the dichroic mirror 16. The transmitted light in this wavelength band passes through the dichroic mirror 16, passes through the Wollaston prism 39 and an analyzer (not shown), and is taken into the imaging device 26. In this case, the two linearly polarized lights that make up the transmitted light are transmitted through the Wollaston prism 39 and the analyzer, so that the wavefront interferes to produce light and dark. The observation light is subjected to differential interference.

  The fluorescent illumination driving circuit 45 turns on or off the excitation light source 11 and opens / closes the shutter 13. The transmitted illumination drive circuit 46 turns on the light source 30 or turns off the light source 30 and opens / closes the shutter 32. The filter drive mechanism 47 switches the excitation filter 14, the fluorescence filter 19, and the absorption filter 20 used during fluorescence observation. The stage drive mechanism 48 moves the stage 38 in the Z-axis direction in addition to moving the stage 38 along the XY plane.

  The microscope 10 includes a CPU 55, a ROM 56, and a RAM 57. The CPU 55 controls each part of the microscope 10 by executing each program stored in the ROM 56. Reference numeral 58 denotes an I / O port, and the external input device 75 is electrically connected to the microscope 10 via the I / O port 58.

As shown in FIG. 2, ROM 56 is an initialization program 60, a main control program 61, instrumentation置制control program 62, recipe control program 63, programs such as a communication control program 64 is stored.

Instrumentation置制control program 62, for example, switching control of the excitation filter, such as movement control of the stage 38, a program used when the actuating separately each part of the microscope 10. The recipe control program 63 is a program used when observing or imaging a specimen using any of imaging conditions registered in advance. Examples of the imaging conditions registered in advance include imaging conditions at the time of observation or specimen image acquisition performed in the past, and imaging conditions input by an external input device. The communication control program 64 is a program used when executing information input / output with an external input device.

  The RAM 57 is partitioned into a plurality of areas. The plurality of areas include an area used when the program is executed, such as an initialization use area 66, a main control storage area 67, an apparatus control use area 68, and a communication control storage area 69, and a control information storage. An area 70, a control position information storage area 71, and other areas in which information is stored.

  In the control information storage area 70, control information when the specimen 18 is observed and imaged, and control information based on the imaging conditions input by the external input device are individually stored. The control information includes an operation control code used when controlling each part of the microscope 10, a control code for simultaneously operating each part of the microscope when controlling the microscope using these operation control codes, and each part of the microscope. Examples thereof include a control code for continuously operating and a weight control code for starting the next operation after each part of the microscope is finished. These control codes may be control codes input in advance from the external input device 75, or may be stored control codes for specimen images acquired previously.

In the control position information storage area 71, position information when a specimen image is acquired and position information output from an external input device are stored for each imaging condition.
The external input device 75 is operated when inputting imaging conditions for imaging the specimen 18 or operating each part of the microscope 10 individually.

  Next, a processing flow of the external input device 75 performed from the input of imaging conditions to the acquisition of a specimen image will be described. As shown in FIG. 3, after placing the specimen 18 stained with a fluorescent reagent on the stage 38, the user inputs imaging conditions using the external input device 75 (step S1). When the imaging condition is input, control information is generated by the external input device 75 (step S2), and the generated control information is output to the microscope 10 (step S3). Thereafter, when the external input device 75 is operated, a specimen image acquisition process is executed. When the specimen image acquisition process is started, control information indicating the start of control is output from the external input device 75 to the microscope 10 (step S4). When the specimen image acquisition process for all input imaging conditions is executed, control information indicating readout of the specimen image is output from the external input device 75 to the microscope 10 (steps S5 and S6). A specimen image is input to the external input device 75 based on this control information. This sample image is displayed on a display screen (not shown) provided in the external input device 75.

  A flow of processing of the microscope 10 performed from input of imaging conditions to acquisition of a specimen image will be described. As shown in FIG. 4, when the main power supply of the microscope 10 is turned on, an initialization process for each part of the microscope 10 is executed (step S11). After the initialization process, when control information is input from the external input device 75, the control information is analyzed (steps S12 and S13). When the control information is an operation control code based on the imaging condition as a result of analyzing the control information (step S14), the CPU 55 writes the operation control code in the control information storage area 70 of the RAM 57 (step S15). At this time, if the position information is included in the control information, the position information is written in the position information storage area 71 of the RAM 57.

  If the analyzed control information is a control start command indicating the start of control (step S16), a control program corresponding to the control start command is read by the CPU 55, and control of the microscope 10 is executed (step S17). If the analyzed control information is other than the information described above, processing for the control information is executed (step S18). When there is no input of control information output from the external input device 75, the CPU 55 enters a standby state.

  A flow of acquiring a specimen image using a plurality of imaging conditions will be described. As shown in FIG. 5, when the imaging process of the specimen 18 is executed, each part of the microscope 10 is operated according to the imaging condition 1 (step S21). When each part of the microscope 10 is set, the imaging device 26 is activated and imaging of the sample 18 is executed (step S22). After the sample 18 is imaged, the next imaging condition (imaging condition 2) is read out, and each part of the microscope 10 is operated in accordance with the imaging condition 2 (step S23). After this operation, the imaging device 26 operates and imaging of the specimen 18 is executed (step S24). When there are three or more imaging conditions, each part of the microscope is executed in the order of setting processing (for example, step S25) and imaging of the sample 18 (for example, step S26) in accordance with the imaging conditions.

  A flow for controlling each part of the microscope 10 will be described. As shown in FIG. 6, the CPU 55 initializes various parameters for executing the recipe control program 63 (step S31), and executes the recipe control program 63. When the recipe control program 63 is executed, each part of the microscope 10 is controlled while reading the control information stored in the RAM 57. When the control information read from the RAM 57 is an operation control code corresponding to each part of the microscope 10 (step S32), the position information is read from the RAM 57, and the operation control based on the operation control code is executed (step S32). S34).

  If the control information is a weight control code, a wait condition is set, and it is determined whether the wait condition is satisfied. (Steps S35 and S36). As this wait condition, for example, when simultaneous control is performed, all the controls are completed, that is, the longest control time among the control times of a plurality of controls has passed. Is not limited to this. For example, if the control content performed by the simultaneous control does not affect the control content to be executed next, any control of the control content performed by the simultaneous control is performed. It may be a condition that has ended. In this determination, when the weight condition is satisfied, the control information is read (step S37, step S32). If the control information is different from the operation control code and the weight control code, processing corresponding to the control code is performed (step S38). The control code different from the operation control code and the weight control code is, for example, a control code for outputting the image data captured by the imaging device 26 to the external input device 75, or a progress of recipe control. Control code for the above.

As described above, when the control based on the read control information is completed, new control information is read, and each part of the microscope is controlled based on the new control information. Then, when the read control information is an end code for ending the recipe control program 63, the recipe control program 63 ends (step S39). Thus, by storing the control information from the external input device 75 in the microscope 10 in advance, the time from when the information from the external input device 75 is input until the operation control according to the information is executed. Can be omitted. That is, it is possible to shorten the time required to acquire the sample image under one imaging condition.

  FIG. 7 is a timing chart showing a specific example of control contents of the microscope 10 using recipe control. As described above, when control information indicating a control start command is input from the external input device 75 to the microscope 10, recipe control is executed in the microscope 10. In the recipe control, simultaneous control and interlocking control are continuously performed. The control contents of the simultaneous control and the interlock control may be classified in advance or may be classified according to the imaging conditions. In FIG. 7, the interlock control is illustrated to start after a lapse of a predetermined time from the end of the simultaneous control. However, the interlock control is started immediately after the simultaneous control ends. May be. In addition, when the interlock control is executed after a predetermined time has elapsed after the simultaneous control is finished, it is preferable that the predetermined time is set to, for example, several tens μS to several hundreds mS. By providing the predetermined time in this way, it is possible to suppress vibration of the electric device operated by the simultaneous control, and an appropriate specimen image can be obtained.

  The above-described simultaneous control is a control in which a plurality of operation controls are performed simultaneously (in parallel). Examples of the control capable of performing the simultaneous control include electric stage control, vertical movement control, excitation filter control, absorption filter control, and fluorescence filter. Control.

  The electric stage control is a control for moving the electric stage 38 along the XY plane, and the vertical movement control is the electric stage 38 that moves the electric stage 38 up and down along the Z axis to bring the illumination light image into a focus position. It is control to move.

  The excitation filter control, the absorption filter control, and the fluorescence filter control are controls for switching each filter so that a filter in accordance with the imaging condition is arranged on the optical path.

  Since these controls have different corresponding operation times, when these controls are being executed, if simultaneous control is performed so that the next linked control is not executed, the weight control is also performed simultaneously. Executed. The weight control is control for setting a standby time from the start of the simultaneous control to the start of the interlock control and determining whether the standby time has elapsed.

The interlock control is a control that performs a plurality of controls continuously. Examples of the control that can perform the interlock control include shutter control and imaging control. The shutter control is control for retracting the shutter 13 disposed on the optical path from the optical path , and the imaging device 26 is control for imaging the sample illuminated by the excitation light.

  In this way, by making the recipe control control content that combines simultaneous control and interlocking control, it is possible to shorten the specimen image acquisition time under one imaging condition.

  In this embodiment, an example of an upright microscope is taken, but the present invention can also be used for an inverted microscope. Further, the observation is not limited to fluorescence observation, and may be transmission observation (bright field observation, dark field observation) or the like.

  In the present embodiment, the recipe control is composed of two controls, that is, simultaneous control and interlocking control. However, the content of the recipe control is not limited to this, for example, two simultaneous controls. And a combination with interlocking control.

It is the schematic which shows the structure of a microscope. It is the schematic which shows the structure of ROM and RAM. It is a flowchart which shows the flow of a process in an external input device. It is a flowchart which shows the flow of the process in a microscope. It is a flowchart which shows the flow of a process in the case of acquiring a sample image using a some imaging condition. It is a flowchart which shows the flow of recipe control. It is a timing chart which shows the specific example of the control content of the microscope using recipe control.

Explanation of symbols

  DESCRIPTION OF SYMBOLS 10 ... Microscope, 13 ... Shutter, 14 ... Excitation filter, 19 ... Fluorescence filter, 20 ... Absorption filter, 26 ... Imaging device, 38 ... Stage, 55 ... CPU, 57 ... RAM, 70 ... Control information storage area, 71 ... Control Position information storage area, 75 ... external input device

Claims (3)

An imaging device for imaging a specimen;
A plurality of electric devices operating as preparation for imaging the specimen by the imaging device;
A storage unit for storing control information for the imaging device and the plurality of electric devices ;
A control unit that reads out the control information stored in the storage unit, and controls operation of the imaging device and the plurality of electric devices based on the read control information;
The controller is
When the control information read from the storage unit includes control information for simultaneously performing a plurality of operation controls, simultaneous control for simultaneously operating a target electric device among the plurality of electric devices;
When the control information read from the storage unit is composed of control information for continuously performing a plurality of operation controls, the interlock that continuously operates the imaging device and the target electric device among the plurality of electric devices. Control,
When the control information read from the storage unit includes control information that sets a standby time from the start of the simultaneous control to the start of the interlock control and determines whether or not the standby time has elapsed, the simultaneous information A standby control for setting the standby time on the condition that any of the control contents executed in the simultaneous control from the start of the control is completed, and determining whether the set standby time has elapsed;
An electric microscope characterized by performing The electric microscope according to claim 1,
To allow the input of the imaging conditions, an external input device for generating the control information based on the inputted image pickup condition is connected,
The power storage microscope stores the control information generated by the external input device. The electric microscope according to claim 2 ,
The electric microscope characterized in that the control information includes position information set on the basis of the imaging conditions, in addition to control codes provided corresponding to the imaging apparatus and the plurality of electric apparatuses.

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