JP6514508B2 - microscope - Google Patents

Description

  The present invention relates to a microscope.

Conventionally, a microscope provided with a focusing mechanism that electrically drives vertical movement of a stage is known (see, for example, Patent Document 1).
The focusing mechanism of this microscope is rigidly fixed to the microscope body by a screw or the like.

JP-A-8-50247

  However, when the focusing mechanism is rigidly fixed to the microscope main body as in the microscope described in Patent Document 1, if the focusing mechanism is driven to repeat the raising and lowering operation and the stopping operation of the stage, There is a disadvantage that the vibration generated by the inertia of the stage mounted on the focusing mechanism is difficult to converge, and it takes time to acquire an image. Even in the focusing mechanism of the type in which the objective lens is moved up and down instead of the stage, the inertia of the revolver and the objective lens is large, so the problem of vibration is more likely to occur.

  The present invention has been made in view of the above-described circumstances, and it is an object of the present invention to provide a microscope that can repeat image acquisition while rapidly moving the focus position while suppressing the occurrence of vibration.

In order to achieve the above object, the present invention provides the following means.
One aspect of the present invention comprises a microscope body and a focusing mechanism attached to the microscope body, the focusing mechanism comprising a stage on which a sample is placed or an objective lens disposed to face the sample on the stage. The base unit includes an arm unit for holding one of the above, a base unit that supports the arm unit so as to be movable in the vertical direction, and a drive unit that moves the arm unit in the vertical direction with respect to the base unit. A contact portion in direct contact with the microscope body, and a movable portion arranged with a gap in between with respect to the microscope body, the gap dimension being variable by elastic deformation, the base portion of the focusing mechanism And a microscope body interposed between the microscope body and the movable portion. The microscope body is fixed with a vibration isolation member interposed between the microscope body and the movable portion .

  According to this aspect, when the arm unit is moved vertically in the vertical direction with respect to the base unit by the operation of the drive unit and then suddenly stopped, the inertial energy of the stage or the objective lens held by the arm unit causes the arm to Because the vibration isolation member is interposed between the base portion and the microscope main body, the inertial energy transmitted from the arm portion to the base portion is absorbed by the vibration isolation member, so that the vibration can be made quickly. Can converge. That is, even when the lifting and lowering operation and the sudden stop of the arm unit are repeated, the vibration is not sustained, so the arm unit can be stopped at an early stage to shift to the image acquisition operation, and the observation time can be shortened. it can.

In the above aspect, the base portion includes a contact portion in direct contact with the microscope main body, and a movable portion which is disposed with a gap from the microscope main body and in which the gap dimension can be varied by elastic deformation. wherein the damping member is that not sandwiched between the microscope body and the movable portion.
By doing this, the contact portion is brought into direct contact with the microscope main body, whereby the base portion is fixed in a positioned state to the microscope main body, and the movable portion and the microscope main body are elastically deformed by the movement of the arm portion. The inertial energy transmitted to the base portion can be efficiently absorbed by compressing or expanding the vibration isolation member sandwiched therebetween.

Further, in the above aspect, an adjustment unit may be provided to adjust the gap size.
In this way, by adjusting the size of the gap by the operation of the adjustment unit, it is possible to adjust the crushing margin of the anti-vibration member sandwiched in the gap. As a result, the vibration isolation member can be set to an optimal state where the vibration isolation effect can be generated, and the vibration can be attenuated more effectively.

In the above aspect, the vibration isolation member may be made of a resin material.
By doing this, it is possible to damp the vibration of the arm portion due to the drive of the focusing mechanism with a simple configuration.

  ADVANTAGE OF THE INVENTION According to this invention, it is effective in the ability to repeat generation | occurrence | production of a vibration and to repeat image acquisition, moving a focus position rapidly.

It is a front view showing a microscope concerning one reference embodiment as a reference example of the present invention. FIG. 2 is a partially broken plan view showing the positional relationship between the focusing mechanism of the microscope of FIG. 1 and the microscope body. It is a front view showing a microscope according to an embodiment of the present invention. It is a front view showing a microscopic variation Katachirei in FIG. It is a front view showing another modification of the microscope of FIG. It is a front view showing a microscope according to a modification of the embodiment of the present invention. It is a block diagram which shows the microscope of FIG.

A microscope 1 according to a reference embodiment as a reference example of the present invention will be described below with reference to the drawings.
The microscope 1 according to the present embodiment is a fluorescence microscope, and as shown in FIG. 1, includes a microscope body 2, a focusing mechanism 3, and an objective lens 4 supported by the focusing mechanism 3. There is.

  The microscope main body 2 is provided on a main body base 5 and the main body base 5 and deflects excitation light L from a light source (not shown) mounted on a stage 6 and a light source (not shown) and irradiates the sample A via an objective lens 4 A fluorescence cube 7 transmitting fluorescence from the specimen A collected by the objective lens 4; an eyepiece optical system 8 for visually observing the fluorescence transmitted through the fluorescence cube 7; a camera 9 acquiring a fluorescence image Is equipped.

  The focusing mechanism 3 is, as shown in FIG. 2, a base portion 10 fixed to the main body base 5 of the microscope main body 2, and supported so as to be able to move up and down with respect to the base portion 10. The arm unit 11 holds the objective lens 4 and the drive unit 12 moves the arm unit 11 up and down.

The fluorescence cube 7 comprises an excitation filter (not shown) for transmitting a specific wavelength of excitation light L from a light source, and a dichroic mirror (shown for illustration) for deflecting the excitation light L transmitted through the excitation filter and transmitting fluorescence from the specimen A This is an optical element for observing desired fluorescence, which is composed of an absorption filter (not shown) for removing the excitation light L contained in the fluorescence transmitted through the dichroic mirror.
The drive unit 12 includes a motor 13 and a ball screw mechanism 14 for transmitting the driving force of the motor 13 to the arm unit 11.

  In the present embodiment, the base portion 10 of the focusing mechanism 3 is fastened to the main body base 5 by the screws 16 with the flat vibration-proof rubber (anti-vibration member) 15 interposed between the base portion 10 and the main body 5 of the microscope main body 2. It is done. The anti-vibration rubber 15 is made of, for example, a resin material containing an elastomer such as a polyurethane near gel material elastomer, in addition to a general rubber material such as urethane rubber or silicone rubber. The anti-vibration rubber 15 functions as a damper that absorbs energy when it is deformed by receiving a compression force or an extension force.

The operation of the microscope 1 according to the present embodiment configured as described above will be described below.
In order to observe the specimen A using the microscope 1 according to the present embodiment, the excitation light L is emitted from the light source in a state where the specimen A is mounted on the stage 6 and the objective lens 4 is disposed vertically above the specimen A Let The excitation light L emitted from the light source is deflected by the fluorescent cube 7, condensed by the objective lens 4 located vertically below, and irradiated onto the specimen A.

  In the sample A, the fluorescent substance contained in the area irradiated with the excitation light L is excited to generate fluorescence. The generated fluorescence is collected by the objective lens 4, transmitted through the fluorescent cube 7, and can be observed visually by the eyepiece optical system 8, and a fluorescent image can be obtained by the camera 9.

  The fluorescence observation of the specimen A is performed while moving the focal position of the objective lens 4 in the specimen A in the direction of the optical axis S of the objective lens 4. In order to move the focal position of the objective lens 4 in the direction of the optical axis S, the drive unit 12 is operated to transmit the driving force of the motor 13 to the arm unit 11 via the ball screw mechanism 14 and supported by the arm unit 11 The objective lens 4 is raised and lowered.

  When the driving force of the motor 13 is transmitted to the arm unit 11, the arm unit 11 moves up and down, and the focal position of the objective lens 4 moves in the sample A. Therefore, the arm unit 11 is stopped and each position in the optical axis S direction A plurality of fluorescence images over a predetermined depth range of the specimen A are acquired by irradiating the excitation light L and photographing the generated fluorescence in a state in which the focal position is arranged at the point. Thereby, three-dimensional fluorescence observation of the sample A can be performed.

  In this case, in the microscope 1 according to the present embodiment, the focusing mechanism 3 is a microscope main body in a state where the anti-vibration rubber 15 is sandwiched between the base portion 10 of the focusing mechanism 3 and the main body base 5 of the microscope main body 2 Since it is fixed to 2, when the arm unit 11 is moved up and down or stopped by the drive of the motor 13, the inertia energy of the objective lens 4 held by the arm unit 11 and the arm unit 11 15 is transformed.

  Thereby, since the inertial energy which vibrates the arm portion 11 is absorbed by the deformation of the vibration-proof rubber 15, the vibration of the arm portion 11 can be converged early. That is, even if the raising and lowering operation and the stopping operation of the arm unit 11 are repeated by driving the motor 13, the vibration of the objective lens 4 fixed to the arm unit 11 can be converged early and stopped at each position. There is an advantage that fluorescence images can be acquired early.

In the present embodiment, as shown in FIG. 1, the base portion 10 of the focusing mechanism 3 and the main body base 5 of the microscope main body 2 are fixed in a completely separated state by the anti-vibration rubber 15. In the microscope 1 according to an embodiment of the present invention , as shown in FIGS. 3 and 4, the base portion 10 and the main body base 5 are in direct contact with each other.

  That is, in the example shown in FIG. 3, a step is provided on the attachment surface of the base portion 10 to the main body base 5, and the contact portion 17 formed one step higher is provided at a position away from the objective lens 4 of the arm portion 11. In the example shown in FIG. 4, the contact portion 17 is provided at a position close to the objective lens 4 of the arm portion 11.

In these cases, when the contact portion 17 is brought into direct contact with the main body base 5 and fastened by the screw 16, a gap is formed between the portion (movable portion) 18 formed lower one step and the main body base 5 It is configured as described above, and the flat vibration-proof rubber 15 is sandwiched in the gap.
By doing this, since the contact portion 17 of the base portion 10 is fixed in direct contact with the main body base 5, the base portion 10 can be accurately positioned on the main body base 5.

Further, when the main body base 5 is elastically deformed by the inertial energy of the arm portion 11 or the objective lens 4, the movable portion 18 separated from the main body base 5 with a gap is separated from the main body base 5. Since it shrinks or enlarges, it is possible to deform the anti-vibration rubber 15 sandwiched therebetween to absorb inertial energy.
That is, according to the structure of FIG. 3 and FIG. 4, accurate positioning of the base part 10 and effective vibration isolation can be compatible.

Further, as shown in FIG. 5, a bracket (adjustment portion) 19 supported so as to be movable in the thickness direction of the vibration-proof rubber 15 is disposed on the installation surface of the vibration-proof rubber 15 of the main body base 5. By adjusting the position of the bracket 19 according to the amount of fastening of the (adjusting portion), the crushing margin of the anti-vibration rubber 15 may be adjusted.
In this way, the vibration-proof rubber 15 can be brought into intimate contact with both the main body base 5 of the microscope main body 2 and the base portion 10 of the focusing mechanism 3 and by achieving an appropriate crushing margin, inertial energy Can be set to an effective absorbable state.

The crushing margin of the anti-vibration rubber 15 may be determined by dimensions, or the pressing force may be measured and pressed until the desired pressing force is achieved.
Further, although the bracket 19 is movably disposed on the main body base 5 side, the bracket 19 may be movably disposed on the base portion 10 side of the focusing mechanism 3.

  Further, in the present embodiment, although the case where the microscope 1 is a fluorescence microscope using the camera 9 has been described, as shown in FIG. 6, a laser scanning microscope (hereinafter referred to as a laser scanning microscope) using the scan unit 21 instead of the camera 3 It may be switchable to LSM). In this case, as shown in FIGS. 6 and 7, the microscope 1 includes a laser light source 22 that generates a laser beam H, and a scan unit 21 that scans the laser beam H from the laser light source 22.

  The scanning unit 21 has a dichroic mirror 24 for deflecting the laser light H transmitted from the laser light source 22 through the optical fiber 23, and the laser light H deflected by the dichroic mirror 24 in a two-dimensional direction (for example, X, A two-dimensional scanner (XY galvano mirror) 25 for scanning in the Y direction, a confocal lens 26 for collecting the fluorescence transmitted through the dichroic mirror 24, and a confocal pin for passing the fluorescence collected by the confocal lens 26 A hole 27 and a photodetector (for example, a photomultiplier tube) 28 for detecting the fluorescence having passed through the confocal pinhole 27 are provided.

  Specifically, when observation is performed using LSM, the scanner unit 21 is disposed on the optical axis S instead of the camera 9, and the fluorescent cube 7 is separated from the optical axis S. Thereby, the sample A can be irradiated with the laser beam H by making the optical path of the laser beam H coincide with the optical axis S.

  The microscope 1 is connected to a control device (for example, PC) 29 that controls the microscope 1 as shown in FIG. The control device 29 includes a camera 9, a driver 30 for driving the motor 13 of the focusing mechanism 3 and the two-dimensional scanner 25, a signal processing device 31 for processing an output signal from the light detector 28, and the camera 9. A monitor 32 for outputting an image acquired by the microscope 1 is connected.

  The signal processing device 31 performs IV conversion (for example, a buffer) of the fluorescence intensity signal from the light detector 28 by IV conversion, and A converts the signal converted by the IV conversion by A / D conversion. And a D / D converter.

  The controller 29 controls the two-dimensional scanner 25 so as to scan the laser light H two-dimensionally on the sample A. Thereby, the control device 29 combines the intensity signal of the fluorescence from the sample A acquired by the light detector 28 and the scan position information of the two-dimensional scanner 25 inputted to the driver 30 to obtain a scan image in the X and Y directions. Are generated and output to the monitor 32.

  The LSM can acquire a slice image of the focal plane by the confocal effect. By repeatedly scanning in the X and Y directions while shifting the position in the Z direction by the focusing mechanism 3, a bundle (XYZ image) of slice images in a predetermined range of the Z position can be acquired. In this case, coordinated operation of scanning in the X and Y directions and Z position adjustment is performed by the control of the two-dimensional scanner 25 and the focusing mechanism 3 by the controller 29.

  LSM is a scan in the X, Y, Z directions (hereinafter referred to as XYZ scan), in which the focusing mechanism 3 moves intermittently (for example, scans in the X, Y directions in a state of stopping at a predetermined Z position, and then predetermined) Move from the Z position to another position in the Z direction and stop again to repeat scanning in the X and Y directions), so that the vibration of the objective lens 4 converges at an early stage by the deformation of the anti-vibration rubber 15. There is an advantage that fluorescence observation can be performed more efficiently.

In addition, when performing XYZ scan using LSM, a small focusing mechanism (for example, a piezoelectric element drive type precision focusing device) different from the focusing mechanism 3 in the portion to which the objective lens 4 is attached in the arm unit 11 X, Y, and Z scans may be performed while driving the small focusing mechanism to shift the Z position in the Z direction. In this case, the focusing mechanism 3 is stopped.
By doing this, the vibration generated by the operation of the small focusing mechanism is suppressed by the anti-vibration rubber 15, and the speed of the XYZ scan can be increased.

  Further, in the present embodiment, when the microscope 1 is provided with a minute aperture disk scanning type optical system and an image is obtained using the camera 9, a confocal image is obtained using the minute aperture disk scanning type optical system You may do it.

1 microscope 2 microscope main body 3 focusing mechanism 4 objective lens 6 stage 10 base portion 11 arm portion 12 drive portion 15 anti-vibration rubber (anti-vibration member)
17 contact portion 18 movable portion 19 bracket (adjustment portion)
20 screw (adjustment part)

Claims (3)

The microscope body,
And a focusing mechanism attached to the microscope body,
An arm that holds either the stage on which the sample is placed or the objective lens disposed opposite to the sample on the stage; and the base that supports the arm so as to be vertically movable. A driving unit for moving the arm unit in the vertical direction with respect to the base unit;
The base portion includes a contact portion in direct contact with the microscope main body, and a movable portion arranged with a gap from the microscope main body, and in which the gap dimension can be varied by elastic deformation.
The microscope in which the base part of the focusing mechanism and the microscope main body are fixed with a vibration isolation member interposed therebetween, and the vibration isolation member is sandwiched between the microscope main body and the movable portion . The microscope according to claim 1 , further comprising an adjusting unit that adjusts the gap size. The damping member is a microscope according to claim 1 or claim 2 is made of a resin material.

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