JPS6047568B2 - Micromanipulator - Google Patents

Description

[Detailed description of the invention] The present invention relates to a micromanipulator.

For example, the micromanipulator is
This method is known as described in Japanese Patent No. 35. However, in the micromanipulator described in the above publication, the movement directions (X, Y, and Z axes) of the micromanipulator do not match the up, down, left, right, front, and back directions as seen through a microscope, so the operation of the micromanipulation device is difficult. It is extremely difficult even for highly skilled workers, and has the disadvantage that it is difficult to improve work efficiency. In order to solve this drawback, the applicant first filed a patent application in 1973.
No. 3-67461 proposed a micromanipulator in which a micromanipulation device is provided on the optical axis of a condenser that includes a condenser lens that is movable in the direction of the optical axis of an objective lens. According to this micromanipulator, the positioning of the micromanipulation device can be performed by the positioning mechanism of the condenser, and the moving directions of both can therefore be perfectly matched, resulting in significantly improved operability. You can get the advantage of However, if the micro-manipulation device is fixed to the condenser on the optical axis of the condenser,
When the micro-manipulation device is damaged, the entire condenser must be replaced, or the condenser must be removed from the microscope and the micro-manipulation device replaced, which is extremely tedious and troublesome. SUMMARY OF THE INVENTION An object of the present invention is to eliminate the above-mentioned drawbacks and to provide a micromanipulator suitably constructed so that only the micromanipulator can be easily replaced.

In the micromanipulator of the present invention, a vibrator is disposed through a through hole formed in an objective lens, a condenser lens, or an objective and condenser lens movable in the optical axis direction of a microscope,
A micro-manipulation device such as an injection needle and an electrode diagonal is attached to the end of the vibrator on the specimen side in a replaceable manner, and the micro-manipulation device is configured to be movable integrally with the lens in the optical axis direction of the microscope. It is characterized by the fact that

According to such a micromanipulator of the present invention,
If the injection needle or electrode needle is damaged, you can simply replace it with a new one, and it is very convenient because the replacement work can be done easily, and there is no need to replace the entire lens with the vibrator installed. It is extremely economical because there is no

Furthermore, since the micro-manipulation devices can be selectively replaced and installed, there is an advantage that a single microscope can be used to perform multiple inspection items on a single specimen. On the other hand, there are generally a plurality of test items for the test object, and among them, the ion concentration of the test object is the main test item. In this case, a microscope equipped with a micro-manipulation device used for each different inspection item and a microscope equipped with an ion sensor for measuring the concentration of specific ions are prepared for the number of inspection items, and one specimen is examined for one inspection while changing the microscope. Inspecting one by one takes time and is not efficient. In a preferred embodiment of the present invention in such a case, a plurality of through-holes are formed in a lens movable in the optical axis direction of the microscope, and a vibrator is disposed in each of these through-holes. An ion sensor is replaceably attached to the end of one vibrator on the test object side, and the other vibrator is attached to the end of the vibrator on the test object side. Micro-manipulation devices such as injection needles and electrode needles are attached to the end of the vibrator in a replaceable manner.

In this way, if one microscope is equipped with multiple micro-operation devices, including ion sensors, multiple inspection items can be processed simultaneously and in a short period of time, which is extremely convenient! Extremely efficient.

Note that, as an ion sensor used in such a micro-manipulation device, for example, a field effect type ion sensor can be used. The present invention will be described in detail below with reference to the drawings. Figure 1 shows an example 4 of the micromanipulator of the present invention.
FIG. The condenser 1 includes a condenser 3 and a phase plate 4 held on a mirror surface 2, and is supported by a holding member 5. This holding member 5 is configured to be movable in the optical axis direction of the objective lens 6 by a moving mechanism (not shown). Note that the condenser 1 is attached to the holding member 5 so that the optical axis of the condenser lens 3 that constitutes the condenser 1 coincides with the optical axis of the objective lens 6. In this example, a through hole 7 is provided in the condenser 1 along a direction including the optical axis of the condenser lens 3.
is formed, and a vibrator 8 is provided to extend into this through-hole portion 7.
Note that one end of the vibrator 8 is slightly protruded from the condenser 1 on the objective lens 6 side, and the other end is fixed by a suitable fixing member 9 provided on the holding member 5. In this way, by passing the vibrator 8 through the condenser 1, micro-manipulation devices such as injection needles and electrode needles can be detachably attached to the end of the vibrator on the objective lens 6 side. It becomes possible to replace and install micro-manipulation devices of the same or different types.

Figure 1 shows an injection needle 10 attached to the end of the vibrator 8 on the objective lens 6 side.
The micromanipulator is equipped with a micromanipulator for supplying or suctioning a predetermined liquid to a specimen 13 in a shear dish 12 placed on a stage 11.

In this case, although not shown, a pipette or the like is attached to the end of the vibrator 8 opposite to the end to which the injection needle 10 is attached. In this example, the vibrator 8 extends in the condenser 1 in a direction that includes the optical axis of the condenser lens 3, so the center of the vibrator 8 must be aligned with the optical axis of the condenser lens 3. For example, the tip of the attached injection needle 10 is also aligned with the optical axis of the condenser lens 3, that is, the objective lens 6.
This will coincide with the optical axis of Therefore, there is no need to perform centering separately. Here, while observing with a microscope, the holding member 5 and/or the stage 11 are moved in the optical axis direction of the objective lens 6, and the tip of the injection needle 10 is inserted into the specimen 13 to perform a predetermined injection or suction operation. You can do this. In FIG. 1, the vibrator 8 is fixed to the holding member 5 by the fixing member 9, so the vibrator 8 in the through-hole portion 7 may be in a fixed state or in a loosely fitted state. FIG. 2 is a diagram showing a modification of the vibrator constituting the micromanipulator of the present invention.

The vibrator 15 shown in this example is particularly suitable for attaching replaceable electrode needles, has at least the inner surface formed of an insulating material, and has an end facing toward the object to be examined (shown in the figure). 1
5" is smaller than the outer diameter of the electrode needle 16 to be attached. In this way, the electrode needle 16 can be inserted through the vibrator 15 from the end of the vibrator 15 on the opposite side to the specimen side. It is possible to attach the electrode needle in a replaceable manner, and it is also possible to effectively prevent the tip of the electrode needle from wobbling when attached.

FIG. 3 is a sectional view showing the configuration of another example of the micromanipulator of the present invention.

In the micromanipulator shown in this example, a through-hole is formed in the condenser of the microscope, and a vibrator is arranged in the through-hole, so that the micro-manipulation device can be attached to it in a replaceable manner, as shown in Fig. 1. In this example, the vibrator was made movable in a plane perpendicular to the optical axis of the light collector in a through-hole formed in the light collector. In FIG. 3, a condenser lens 21 is supported by a lens barrel 22, and this mirror surface 22 is fixed with a screw 24 to a holding member 23 movable in the optical axis direction of the microscope. Also, phase plate 2
5 is supported by a fixing screw 27 on a cylindrical member 26 screwed onto the lens barrel 22, and can be manually positioned relative to the condenser lens 21 by loosening the fixing screw 27. Make it. Further, a through hole 28 centered on the optical axis of the condenser lens 21 is formed in the condenser lens 21 and the phase plate 25 . In this example, the diameter of the through-hole 28 is made slightly larger than the outer diameter of the vibrator to be disposed, so that the vibrator can move within the through-hole 28 in a direction perpendicular to the optical axis. Furthermore, a cylindrical vibrator holding member 30 is provided in engagement with the cylindrical member 26 for centering the vibrator disposed therein. This vibe holding member 30 includes a portion 31 that comes into contact with the cylindrical member 26,
A portion 32 having an inner diameter larger than the outer diameter of the cylindrical member 26 extends along the outer periphery of the cylindrical member 26, and for example, three centering screws 33 are provided on the outer periphery of the portion 32. They are screwed so that their tips abut against the outer circumferential surface of the cylindrical member 26. Furthermore, a vibrator 35 made of stainless steel or the like having an outer diameter smaller than the diameter of the through-hole portion 28 is fixed to the vibrator holding member 30 through a light-transmitting member 34 such as an acrylic plate. extending through hole 28. In FIG. 3, the vibrator holding member 30 can be moved in a direction perpendicular to the optical axis of the condenser lens 21 by adjusting the centering screw 33.

At this time, the vibrator 35 is fixed to the holding member 30 and is loosely fitted in the through hole 28, so it moves together with the holding member 30 in a direction perpendicular to the optical axis. Therefore, if the center of the micro-manipulation device (not shown) attached to the tip of the vibrator 35 is shifted due to replacement, etc., the centering screw 33 can be easily adjusted. Therefore, centering can be easily performed. Fourth
The figure is a sectional view showing the configuration of still another example of the micromanipulator of the present invention. In this example, in the micromanipulator shown in FIG. 1, a through-hole 37 is further formed in the condenser 1, a vibrator 38 is similarly arranged therein, and an ion sensor is attached to the end of the vibrator on the objective lens side. 40 is attached replaceably. In this way, by providing the ion sensor 40 and injection needle 10 in one microscope, two
It is extremely efficient because tests for various items can be processed simultaneously or in a short period of time.

Note that as the ion sensor, for example, an ion sensor that utilizes the electric field effect of a semiconductor developed in recent years can be used. These ion sensors have much superior characteristics, such as response speed, selectivity, and miniaturization, compared to ion sensors that use glass electrodes that have been widely used in the past, and are capable of measuring ion changes on the surface of cell membranes. It can be used fully. As described above, according to the present invention, the micro-manipulation device is not directly fixed to the lens movable in the optical axis direction of the microscope, but a through-hole is formed in the lens, and the through-hole is inserted into the lens. Because I glued it to the vibrator that was placed,
When the micro-manipulating device is damaged, only the micro-manipulating device can be easily replaced without replacing the entire lens with a lens equipped with a new micro-manipulating device or removing the lens from the microscope.

Note that the present invention is not limited to the above-mentioned example, and can be modified or changed in many ways.

For example, in all of the above-mentioned examples, a through-hole is formed in the condenser and the micro-manipulation device is attached thereto, but it is also possible to form a through-hole in the objective lens and attach it thereto. Furthermore, it can be effectively implemented not only in a transmission type microscope but also in an epi-reflection type microscope. Furthermore, any number of through-holes may be formed as long as the necessary minimum amount of illumination light and observation light amount are ensured. In this case, different micro-manipulation devices or devices of the same type can be attached, so the selection can be made as appropriate depending on the number of objects to be examined and the inspection items.

[Brief explanation of drawings]

FIG. 1 is a sectional view showing the configuration of an example of the micromanipulator of the present invention, FIG. 2 is a diagram showing the shape of another example of the vibrator used in the invention, and FIG. 3 is a diagram showing another example of the micromanipulator of the invention. FIG. 4 is a sectional view showing the structure of another example. DESCRIPTION OF SYMBOLS 1... Condenser, 2... Lens barrel, 3... Condenser lens, 4... Phase plate, 5... Holding member, 6... Objective lens, 7... Through-hole part , 8...vibrator, 9...
Fixing member, 10... Injection needle, 11... Stage, 1
2... Sheare, 13... Test object, 15... Vibrator, 16... Electrode needle, 21... Condenser lens,
22... Lens barrel, 22... Holding member, 24... Screw, 25... Phase plate, 26... Cylindrical member, 27...
Fixing screw, 28... Through-hole portion, 30... Vibe holding member, 33... Centering screw, 34... Light transmitting member,
35... Vibrator, 37... Through-hole portion, 38... Vibrator, 40... Ion sensor.

Claims (1)

[Scope of Claims] 1. A pipe is provided through a through hole formed in an objective lens, a condensing lens, or an objective and condensing lens movable in the optical axis direction of the microscope, and the end of the pipe on the object side 1. A micromanipulator, wherein micromanipulators such as injection needles and electrode needles are replaceably attached to the part of the micromanipulator, and the micromanipulators are configured to be movable integrally with the lens in the optical axis direction of the microscope. 2. In the through-hole section, the pipe is movable relative to the lens in a plane perpendicular to the optical axis of the microscope, or in this plane and in the direction of the optical axis of the microscope, so that the micro-manipulation device can be centered. The micromanipulator according to claim 1, characterized in that: 3. The micromanipulator according to claim 1, wherein at least one inner surface of the pipe is formed of an insulating member, and an electrode needle can be attached through the pipe. 4. A plurality of the through-holes are formed, a pipe is disposed in each of the through-holes, and an ion sensor is replaceably attached to the end of at least one pipe on the test object side. The micromanipulator according to claim 1, characterized in that: