JP3293189B2 - Micro manipulator system - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a micromanipulator system, and more particularly to a micromanipulator system provided with a microscope and a micromanipulator for three-dimensionally manipulating a microscopic sample within the field of view of the microscope.

[0002]

2. Description of the Related Art For example, when a DNA solution is injected into a cell, a micromanipulator system including a micromanipulator having a microneedle on one side and a capture needle on the other side, and a microscope for observing the operation contents. Is used. In a general micromanipulator system, an image is displayed on a CRT display or the like by operating a small instrument such as a small needle or a capture needle in a visual field of a microscope, and is placed in a container such as a petri dish while observing the displayed contents. A predetermined process is performed on a minute sample such as a cell.

In this type of micromanipulator system, for example, a joystick for X and Y axes that can be tilted back and forth and left and right, and a rotary dial for Z axis are operated with both hands to operate in three axial directions in a space. The micromanipulator is minutely operated (in the X, Y, and Z axis directions).

[0004]

In the above-mentioned conventional configuration,
With respect to the positional relationship between the micro sample and the micro device, the positional relationship within the horizontal axis can be determined while looking at the display screen. However, the only way to know the positional relationship in the Z-axis direction (height direction) is to judge from the degree of defocus. For example, by focusing on a micro sample and then focusing on a micro instrument, the positional relationship in the height direction is determined. For this reason, skill is required to determine the positional relationship in the height direction, and many operators do not understand this positional relationship in the height direction.
This is an obstacle to operation, and is a factor that hinders improvement in operability of the micromanipulator.

An object of the present invention is to improve the operability of a micromanipulator.

[0006]

A micromanipulator system according to the present invention includes a microscope, a micromanipulator, imaging means, and display means. The micromanipulator three-dimensionally manipulates a micro sample in a container within a field of view of a microscope. The imaging means captures an image in the field of view. The display means includes a picked-up image obtained by the imaging means, a height position of the tip of the microsample and the micromanipulator, a microsample , a bottom position of the container, and a microphone.
Mark each mark on the tip of the Roman manipulator
Is displayed in correspondence with the position of .

[0007]

In the micromanipulator system according to the present invention, the image picked up by the image pickup means and the height position of the micro sample and the tip of the micromanipulator are displayed by the display means. Thereby, the positional relationship between the micromanipulator and the minute sample in the horizontal axis and the positional relationship in the height direction are displayed. Therefore, the positional relationship in the height direction between the micro sample and the tip of the micromanipulator can be easily determined, and the operability of the micromanipulator is improved. Ma
In addition, this system, in addition to the above,
At the bottom of the robot and at the tip of the micromanipulator
Are displayed corresponding to the respective positions. did
Therefore, the positional relationship between the micro sample and the micromanipulator
The tip of the micromanipulator is not only the
It is possible to prevent damage due to collision with the bottom.

[0008]

FIG. 1 shows a micromanipulator system according to an embodiment of the present invention. In the figure, a micromanipulator system controls a microscope 2 mounted on a base 1, a pair of micromanipulators 3 and 4 arranged on both sides of the microscope 2, and a microscope 2 and micromanipulators 3 and 4. And a control device 5.

The microscope 2 has an operation table 6 at the center thereof, and a petri dish 7 for accommodating a small sample such as a cell is arranged on the operation table 6. An objective lens (not shown) is arranged below the operation console 6, and a TV camera 9 is connected to a lower end of the objective lens. The operation console 6 can be driven in a horizontal direction (X, Y axis directions) and a vertical direction (Z axis direction) by a drive mechanism (not shown).

The micromanipulators 3 and 4 are mounted on a base 1 and have tables 10 and 11 and tables 10 and 11.
Coarse moving parts 12 and 13 separately mounted on the fine moving parts 12 and 13 and fine moving parts 14 and 15 separately mounted on the coarse moving parts 12 and 13
And mainly. The coarse movement units 12 and 13 can move the tables 10 and 11 in the X, Y and Z axis directions in units of several tens of μm by pulse motors (not shown). The fine moving units 14 and 15 are formed by the coarse moving units 12 and 1 by an electromagnetic force method.
3 can be moved in units of 1 μm in the X, Y, and Z axis directions. Arms 16 and 17 driven by the fine movement units 14 and 15 are separately provided at the end of the fine movement units 14 and 15 on the microscope 2 side. An injection pipette 18 is attached to the tip of one arm 16. A suction pipette 19 is attached to the other arm 17. Both pipettes 18, 19 have cylinders 20,
21 are separately connected via tubes 22 and 23.

The control device 5 mainly has a monitor 24, an operation panel 25, and a control unit 26. The operation panel 25 includes a joystick 2 for finely moving the two micromanipulators 3 and 4 separately in the X and Y axis directions.
7, 28, fine movement dial 29, 3 for fine movement in the Z-axis direction
0, and coarse movement keys 31 and 32 including an up-down key and a cursor key for coarsely moving in the X, Y, and Z axis directions, and a numeric keypad 3 used for inputting a cell size, which will be described later.
3, an adsorption key 34 operated at the time of cell adsorption, and other keys.

As shown in FIG. 2, the control unit 40 constituting the control unit 26 comprises a microcomputer including a RAM, a ROM and the like. The control unit 40 includes a TV camera 9, an operation panel 25, a micromanipulator 3,
4, drive units 41 and 42 for driving the respective motors and electromagnetic force units in three axial directions, a memory 43 for storing various set values, a video RAM 44, and a video RA.
An adder 45 for superimposing the output of M44 and the image captured by the TV camera 9 is connected. In the video RAM 44, information for displaying a scale corresponding to the magnification, a mark indicating a positional relationship in the Z-axis direction described later, and the like are stored corresponding to the display position. The monitor 24 for displaying a superimposed image is connected to the adder 45.

Next, the operation of the above embodiment will be described with reference to the control flowcharts of FIGS. The control unit 40 performs an initial setting in step S1 of FIG. Here, for example, the coarse moving parts 12, 13 and the fine moving parts 14, 15 are set to the initial positions. In step S2, it is determined whether to perform the setting process. In step S3, a display process is performed.
The details will be described later. In step S4, it is determined whether one of the joysticks 27 and 28 has been operated. In step S5, it is determined whether any of the cursor keys has been operated. In step S6, it is determined whether or not one of fine movement dials 29 and 30 has been operated. In step S7, it is determined whether any of the up / down keys has been operated. In step S8, it is determined whether another key has been operated. If the determination in step S8 is NO, the process moves to step S9. In step S9, other processing is performed, and the process returns to step S2.

Here, assuming that the joysticks 27 and 28 are operated, the program shifts from step S4 to step S30. In step S30, fine movement units 14 and 1 are operated according to the operation direction of the operated joystick.
5 is slightly moved in the X and Y axis directions. If it is determined in step S5 that the cursor key has been operated, the process proceeds to step S31.
Move to In step S31, the coarse movement units 12, 13 are coarsely moved in the X and Y axis directions. If it is determined in step S6 that fine movement dials 29 and 30 have been operated, step S32 is performed.
Move to In step S32, fine movement units 14 and 15 are finely moved in the Z-axis direction. If it is determined in step S7 that the up / down key has been operated, the process proceeds to step S33. In step S33, the coarse moving parts 12, 13 are coarsely moved in the Z-axis direction. If it is determined in step S8 that another key has been operated, the process proceeds to step S34. In step S34, other key processing corresponding to the pressed key is performed.

On the other hand, when the setting process is instructed, the program shifts from step S2 to step S10. In step S10, the setting process shown in FIG. 4 is performed. Here, first, in step S11, the input of the cell size by the ten keys 33 is accepted. This cell size is the diameter of a cell determined with reference to a scale or the like displayed in superimposition.

In step S12, a reference height setting operation is performed. Here, by operating the fine movement dials 29, 30 and the up / down keys, the pipettes 18, 19 are brought into contact with the bottom of the petri dish 7, and a process of setting the reference height is received. Here, the positions where the pipettes 18, 19 contact the bottom surface of the petri dish 7 are stored in the memory 43 as reference positions of the respective micromanipulators.
In step S13, other setting processing is performed, and the process returns to the main routine.

In the display process of step S3 in FIG.
In step S21, an image captured by the TV camera 9 is displayed. In step S22, the positions of the manipulators 3 and 4 in the Z direction are read. In step S23, the height of the tip position of the micropipettes 18, 19 of the micromanipulators 3, 4 is calculated based on the read position in the Z direction and the reference height set in step S14. Further, the center position in the height direction of the cell is determined based on the cell size input in step S11 on the assumption that the cell is spherical. For example, as shown in FIG. 6, when the diameter of the cell 45 at the bottom of the petri dish 7 is a and the reference height is c, the center height h of the cell is (c + a / 2).
Becomes On the other hand, the center position h of the cell 46 moved upward by b by the suction pipette 19 is (c + a / 2 + b).
Becomes If the injection pipette 18 is similarly moved upward from the bottom of the petri dish d, the tip position is (c + d).

In step S24, it is determined whether or not the cells are being sucked by the suction pipette 19 based on whether or not the suction key 34 is operated. If it is determined that the cells are adsorbed, the process proceeds from step S24 to step S2.
Move to 6. In step S26, a cell mark 50 indicated by a circle is displayed at the upper right corner of the display screen of the monitor 24, as shown in FIG. This display position corresponds to the tip position of the suction pipette 19.

If it is determined in step S24 that the suction key 34 has not been sucked, the flow proceeds to step S25. In step S25, the cell mark 50 is displayed at a position corresponding to the position of the cell placed on the bottom of the petri dish 7. When the display processing in step S25 or S26 is completed, the process proceeds to step S27. In step S27, the tip mark 51 of the injection pipette 18 is displayed. In step S28, a bottom position mark 52 indicating the bottom position of the petri dish 7 is displayed. The display positions of these marks are displayed based on the positions calculated in step S23. In addition, the height position is displayed on the micron order beside this mark.

Here, since the positional relationship between the cells and the injection pipette 18 in the height direction is schematically displayed, for example, the injection pipette 18 can be easily inserted into the cells. The display of this mark is switched substantially in real time each time the pipettes 18 and 19 are operated, so that the current positional relationship in the height direction is always displayed on the monitor 24.

[Other Embodiments] (a) If an automatic setting function for making the center position of the cell equal to the position of the tip of the pipette in the height direction is further provided, the cell processing can be performed by operating the manipulator. When performing the operation, the operation can be completed by performing only the operation in the horizontal plane, and the skill in inserting the pipette into the cell is not required.

Further, if an automatic setting function for making the position eccentric from the center of the cell equal to the position of the tip of the pipette in the height direction is further provided, an arbitrary setting not in the center of the cell but in the height direction of the cell is provided. The pipette can be automatically stabbed at the position. (B) When setting the reference position in the height direction, a configuration may be employed in which the position in the height direction is grasped on the microscope main body side. Here, for example, a vertical position detection device is provided on the microscope 2 side, the bottom position of the petri dish is focused, read by this position detection device, and further, the focus knob of the microscope is moved to move the tip of the pipette and the position of the cell. Focus on and grasp the position in the height direction on the microscope body side. In this case, it is not necessary to bring the tip of the pipette into contact with the petri dish, and it is possible to prevent the tip of the pipette from being damaged.

Further, a configuration may be adopted in which the pipette is brought into contact with the upper end of the cell to detect the positional relationship between the cell and the tip of the pipette.

[0024]

In the micromanipulator system according to the present invention, the display means displays the picked-up image, the minute sample, and the height position of the tip of the micromanipulator. As a result, the positional relationship between the micro sample and the tip of the micromanipulator can be grasped three-dimensionally by displaying the height image and the plane image obtained by imaging, and the operability of the micromanipulator is improved. In addition, in this system, the display hand
Steps are for microsamples, container bottoms and micromanipulators.
Each mark at the tip of the data corresponds to each position
Is displayed, so the tip of the micromanipulator
Can prevent damage by hitting the bottom of the container
You.

[Brief description of the drawings]

FIG. 1 is a perspective view of a micromanipulator system according to one embodiment of the present invention.

FIG. 2 is a block diagram of the control unit.

FIG. 3 is a control flowchart of a control unit.

FIG. 4 is a control flowchart of a control unit.

FIG. 5 is a control flowchart of a control unit.

FIG. 6 is a schematic sectional view showing the positional relationship between a pipette and cells.

FIG. 7 is a diagram showing an example of a display.

[Explanation of symbols]

 2 Microscope 3, 4 Micromanipulator 5 Control device 9 TV camera 24 Monitor 26 Control unit 40 Control unit

Claims (1)

(57) [Claims] A microscope; a micromanipulator that three-dimensionally manipulates a micro sample in a container within a field of view of the microscope; an imaging unit that captures an image within the field of view; and an image captured by the imaging unit. The height position of the tip of the micro sample and the micro manipulator ,
Micro sample, container bottom position and micro manipulator
Display means for displaying each mark at the tip corresponding to each position .