JPH0622743A - Mechanism for transporting cell - Google Patents

Abstract

PURPOSE:To obtain a device having a mechanism capable of removing cells contained in an isolated state in a solution in a proper direction and collecting by setting a flat board to be driven by an electrostrictive element in a chamber, impressing an unsymmetrical waveshape voltage to the electrostrictive element to drive the flat board. CONSTITUTION:A flat board 13 to be driven by an electrostrictive element 11 is set in a chamber 9 to be charged with a solution containing cells and an unsymmetrical waveshape voltage is impressed to the electrostrictive element to drive the flat board. A control circuit 18 to regulate the driving circuit of the electrostrictive element subjects a picture signal of a video camera 16 to image processing and regulates the waveshape, period, amplitue, etc., of the driving circuit.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention separates cells that are isolated and contained in a liquid phase and settled on the bottom surface of a container to a predetermined position or a desired position on the bottom surface of the container. The present invention relates to a cell transfer device that enables operations such as picking up to a cell.

[0002]

2. Description of the Related Art In the field of so-called biotechnology, techniques for growing new varieties of plants by cell fusion have been developed. In such a field, various technical difficulties have been pointed out because extremely minute cells isolated in a liquid phase are handled. Conventionally, as a means for handling such cells, one using a micromanipulator as shown in FIG. 9 is known.

In FIG. 9, a petri dish 3 is placed on a movable table 2 supported by a spindle 1 of a microscope, a solution 4 containing isolated cells is placed in the petri dish 3, and the petri dish 3 is provided above the spindle 1. The cells are visually recognized with a high-magnification optical system (not shown). Further, the micromanipulator 5 is provided at one end of the microscope, and the micromanipulator 5 is moved by the operating mechanism 6 in the front-back direction (longitudinal direction) a, the vertical direction b,
It is movable in the left-right direction c and can be further rotated along the axis by an arbitrary angle θ.

As shown in FIG. 10, an extremely thin glass thin tube 7 formed by pulling the glass tube while heating it in a flame at a high temperature is attached to the tip of the micromanipulator 5, and the end of the glass thin tube 7 is attached. A suction means such as a suction pump or a syringe is connected to the section. Then, when a person finds an appropriate cell with a microscope and brings the tip of the glass tube 7 close to the cell by operating the operating mechanism 6, the cell can be adsorbed by the suction force due to the negative pressure of the tip opening. The cells were collected and moved by the operation.

[0005]

However, in such a conventional cell transfer device, the thin glass capillary attached to the tip of the micromanipulator is complicated because it is damaged by a slight impact. In addition, there is a problem that an operation such as bringing the tip portion of the micromanipulator close to the cell while operating the microscope requires extremely high skill, and it takes a long time to perform one sampling operation.

Further, since such manual work requires skill, the operation efficiency is deteriorated, and it is extremely difficult to process live cells rapidly and to process a large amount of sample. Further, since the cells are adsorbed and collected by suction using the glass thin tube, there is a problem that the cells are easily damaged by a physical external force caused by suction.

The present invention has been made in view of the above-mentioned conventional problems, and it is possible to move / collect a large amount of cells contained in a solution in an isolated state in a suitable direction. The purpose is to provide a device.

[0008]

In order to achieve such an object, the present invention provides a flat plate driven by an electrostrictive element in a chamber and drives the electrostrictive element by applying an asymmetric waveform voltage. Therefore, the cells contained in the solution in the chamber are moved in an arbitrary direction and position by making the moving speed of the plate in the forward direction different from the moving speed in the backward direction.

[0009]

According to the cell moving device of the present invention having such a structure, the moving speed of the flat plate in the forward direction and the moving speed in the backward direction are different, so that the moving amount of the cells by the flat plate depends on the speed difference. A difference is caused, and the cells can be gradually moved in the direction of the difference without damage.

[0010]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS An embodiment of the cell migration device according to the present invention will be described below with reference to the drawings. 1 is a plan view when the apparatus is viewed from above, FIG. 2 is a sectional view taken along the line AA of FIG. 1, and FIG. 3 is a perspective view having a sectional view taken along the line BB of FIG. First, the configuration will be described. 8 is a casing of the apparatus, and a chamber 9 is formed by integral molding or the like. A first electrostrictive element 11 is fixed to one end of the chamber 9, and a second electrostrictive element 12 is fixed to the other end perpendicular to the one end.

Reference numeral 13 denotes a flat plate disposed on the bottom surface of the chamber 9, one end of which is fixed to one end of the first electrostrictive element 11,
The other side end perpendicular to the side end is fixed to one end of the second electrostrictive element 12. That is, the flat plate 13 is supported at the side end of the chamber 9 via the first and second electrostrictive elements 11 and 12. Reference numeral 14 is a drive circuit that outputs a drive voltage V1 for driving the first electrostrictive element 11, and 15 is a second electrostrictive element 1.
2 is a drive circuit that outputs a drive voltage V2 for driving 2.

Reference numeral 16 denotes a video camera provided on the chamber 9 for monitoring the inside of the chamber 9. 17
Is an illumination lamp for setting the optimum exposure for shooting by the video camera 16. Reference numeral 18 denotes a control circuit for controlling the operation of the entire apparatus, which receives a video signal AV from the video camera 16 to monitor the situation of cell migration processing described later and the operation of the drive circuits 14 and 15. And outputs a control signal S for controlling. The control circuit 18 is provided with arithmetic means such as a microprocessor and is adapted to perform automatic control by a program.

When the crossing voltage V1 is supplied to the first electrostrictive element 11, the first electrostrictive element 11 deforms toward the flat plate 13 side (X direction) according to the frequency and the waveform of the crossing voltage V1. The electrostrictive element 12 is a flat plate 1 according to the frequency and waveform of the crossing voltage V2.
It deforms to the 3 side (Y direction). Therefore, the voltage V
By controlling the frequencies and waveforms of 1 and V2, the flat plate 13 can be vibrated in the X direction, the Y direction, or any direction therebetween.

Next, the operation of this embodiment having such a configuration will be described. First, a solution containing the isolated cell group is placed in the chamber 9. Then, after confirming that the cell group has settled on the flat plate 13, the device is moved over. FIG. 4 shows the driving circuit 14
Shows a waveform of the voltage V1 applied to the first electrostrictive element 11, and has a short rising period An in the first half of each cycle Tn and a long falling period Bn in the second half, which is an asymmetrical triangle, and has a period Tn. This voltage V1 is continuously applied to the first electrostrictive element 11.

The first electrostrictive element 11 has a period An.
In, the flat plate 13 is moved at a high speed in the X direction at a high speed, and the flat plate 13 is pulled back in the opposite direction at a low speed by repeating the contraction at a low speed in the period Bn. As a result, the cell group settling on the bottom surface of the flat plate 13 is unable to follow the high-speed movement of the flat plate 13 in the period An, and thus stays at the original position, and in the next period Bn, the flat plate 13 is moved. When the cells return at a low speed, the cell groups move together due to contact friction with the bottom surface of the flat plate 13. Then, by continuously performing this operation, the cell group can be gradually moved to the first electrostrictive element 11 side.

FIG. 5 shows another waveform of the voltage V1. When the voltage V1 having this waveform is applied to the first electrostrictive element 11, an effect opposite to that of the voltage V1 having the waveform shown in FIG. 4 is obtained. That is, the voltage rises at a low speed in the first half period An of the cycle Tn, and drops at a high speed in the second half period Bn. Therefore, during the period An, the flat plate 13 moves at a low speed so that the cell group also follows and moves in the same direction, and during the period Bn, the flat plate 13 returns at a high speed, and the cell group cannot follow due to its own inertia. Due to the movement, the cell group gradually becomes the first
It moves away from the electrostrictive element 11.

Although the operation of only the first electrostrictive element 11 has been described, the same voltage V as these waveforms is applied to the second electrostrictive element 12.
The same function is exhibited by applying 2. That is, when the voltage V2 having the waveform shown in FIG. 4 is applied to the second electrostrictive element 12, the cell group can be gradually attracted to the second electrostrictive element 12 side, and the voltage V2 having the waveform shown in FIG. When applied, the cell group can be moved away from the second electrostrictive element 12.

Further, by simultaneously applying voltages V1 and V2 having asymmetric waveforms to the first and second electrostrictive elements 11 and 12, the cell group can be moved in an arbitrary direction between the X direction and the Y direction. You can The setting of such a moving direction is performed by the control circuit 18 by the video signal A obtained by the video camera 16 capturing an image.
V is subjected to image processing, and the drive circuit 14, based on the processing result,
The periods An and Bn of the waveforms of the 15 output voltages V1 and V2, the period Tn, and the amplitude are automatically adjusted. That is, the control circuit 18
When the operator inputs a desired cell size, shape, etc. with an input device (not shown), this data is stored inside, and from the video signal AV from the video camera 16, the cells corresponding to the specified standard are stored. Identify the location. Then, in order to move to a predetermined position of the chamber 9 and collect it, the distance and the direction between the position of the cell and the position to be moved are detected, and the voltage of the waveform capable of operating the flat plate 13 in the detected direction. V1 and V2 are applied to the first and second electrostrictive elements 11 and 12. Then, the designated cell is moved to a predetermined position by repeatedly performing feedback control of the analysis of the video signal and the movement control of the flat plate 13.

The control circuit 18 previously contains a plurality of types of data relating to the voltage waveform periods An and Bn for determining the moving direction of the flat plate 13 and the voltage amplitude for setting the moving amount, Based on the result of the above video signal processing, these optimum data are selected, and the drive circuits 14 and 15 are selected.
, The voltages V1 and V2 corresponding to the data are generated.

As described above, according to this embodiment, the designated cells can be automatically moved to a desired position, and a collecting means such as a collecting chamber is installed at the desired position. , Can be collected reliably. Further, since it can be moved in the solution, the cells are not damaged. Further, the micromanipulator described in the conventional example can be used in combination, and conventionally, the micromanipulator had to be operated so as to move to the cell side, which was complicated, but the device of the present example was used for manipulating cells. After moving to a predetermined position on the side, it becomes possible to collect with a manipulator, and cells can be collected reliably and without damage.

These are examples of the effects, but the effect of automatically and non-contactingly moving the cells to a desired position is extremely large, and can be used in combination with existing devices and various applications. It is possible. Next, another embodiment will be described with reference to FIG. In FIG. 6, the same parts as those in FIGS. 1 to 3 are indicated by the same reference numerals. In this embodiment, the flat plate 19 having a long groove 20 shallower than the cell diameter is formed on the bottom surface.
It is attached to the second electrostrictive elements 11 and 12. Then, the control means similar to those of the previous embodiment controls the applied voltages V1 and V2 of the first and second electrostrictive elements 11 and 12.

According to this embodiment, when the flat plate 19 is moved back and forth, the cells easily move along the direction α in which the long groove 20 is engraved (the angle between α and X is θ). Furthermore, cells having a size corresponding to the depth of the long groove 20 are likely to collect along the long groove 20. As a result, the accuracy of selecting the designated cells is improved, and reliable control can be realized particularly when the cells are moved to the position of the end portion of the long groove 20.

Further, by providing detachably a plurality of types of flat plates 19 in which the engraving direction α of the long groove 20 is variously set, the voltages V1 and V applied to the first and second electrostrictive elements 11 and 12 are provided.
The control of No. 2 can be further simplified, and the load on the control means can be reduced. Next, still another embodiment will be described with reference to FIG. In FIG. 7, the same parts as those in FIGS. 1 to 3 are indicated by the same reference numerals. In this embodiment, a groove portion having a wide area groove portion 21 and a slit-like narrow groove portion 22 extending in a predetermined direction is formed on the bottom surface of a flat plate 23, and is carved with the respective groove portions 21 and 22 to be shallower than the cell diameter. ing. Then, the first and second electrostrictive elements 11 and 12 are driven by the asymmetrical waveform voltages V1 and V2 applied from the drive circuit, and the flat plate 23 is moved back and forth to move the cells.

According to this embodiment, a plurality of cells are formed in the groove portion 2.
Since the cells gather in 1 and are aligned in the narrow groove portion 22 and pass through the groove portion 22, cells can be moved while being aligned, and precise operations such as collecting and observing individual cells are realized. be able to. Next, still another embodiment will be described with reference to FIG.

This embodiment is a modification of the first embodiment shown in FIGS. 1 to 3, and the same parts as those in the drawings are designated by the same reference numerals. The difference from the first embodiment is that a lattice-shaped blade member 24 is fixedly provided on the opening side of the chamber 9. Further, the blade member 24 is provided so as to be separated from the flat plate 13 by a predetermined distance, so that even if the flat plate 13 is moved in the horizontal direction by the operation of the first and second electrostrictive elements 11 and 12, it is always in the chamber 9. To stand still.

Then, a part or the whole of the lower end portion of the vane member 24 is soaked in the solution containing cells, and the first and second electrostrictive elements 11 and 12 are applied with an asymmetrical voltage from the drive circuit similar to the above. Drive to move the flat plate 13 forward and backward in the horizontal direction. According to this embodiment, the flat plate 13 moves back and forth,
Since the blade member 24 obstructs and attenuates the flow of the solution vibration and the agitation caused by the vibration of the second electrostrictive elements 11 and 12, it is possible to prevent the cells from arbitrarily moving according to the solution flow. As a result, the accuracy of cell migration control can be improved. The shape / structure of the blade member 24 is not limited to this, and any other shape / structure may be used as long as it has the effect of blocking the flow of the solution.

[0027]

As described above, according to the cell migration device of the present invention, a flat plate driven by an electrostrictive element is provided in a chamber, and a voltage having an asymmetric waveform is applied to the electrostrictive element to drive the plate. Since the plate advance / retreat speeds are made different, the cells in the solution containing the cells placed in the chamber can be moved and accumulated in the direction of the advance / retreat speed difference, and the cells can be collected and observed automatically and in a non-contact manner. , And other various processes can be realized.

Further, by providing the flat plate with the groove portion, the cells can be aligned and moved, and an excellent effect is exhibited in various cell treatments.

[Brief description of drawings]

FIG. 1 is a plan view for explaining the structure of a first embodiment.

FIG. 2 is a partial vertical cross-sectional view of FIG.

FIG. 3 is a partial vertical sectional view of still another portion of FIG.

FIG. 4 is a waveform diagram showing a waveform of an applied voltage applied to the electrostrictive element.

FIG. 5 is a waveform diagram showing another waveform of the applied voltage applied to the electrostrictive element.

FIG. 6 is a partial vertical cross-sectional view showing the structure of the second embodiment.

FIG. 7 is a partial vertical cross-sectional view showing the structure of the third embodiment.

FIG. 8 is a partial vertical cross-sectional view showing the structure of the embodiment of FIG.

FIG. 9 is an explanatory view showing the structure of a conventional cell manipulating means.

10 is a partial cross-sectional view for explaining the structure and function of the glass capillary in FIG.

[Explanation of suffix]

 8; Casing 9; Chamber 11; First electrostrictive element 12; Second electrostrictive element 13, 19, 23; Flat plate 14, 15; Drive circuit 16; Video camera 18; Control circuit 20, 21, 22; Groove part 24; blade member

Claims (3)

[Claims] 1. A cell moving device for moving cells in a solution containing isolated cells to an arbitrary position, a chamber for containing the solution, and an electrostrictive element provided on one side of the chamber, A flat plate fixed to one end of the electrostrictive element and housed in the chamber, and an extension and contraction rate of the electrostrictive element are made different by applying a voltage having an asymmetric waveform to the electrostrictive element. A driving circuit for reciprocating the moving speed in one direction and the backward moving speed is different, and the cell is moved to an arbitrary direction and position by a difference in moving speed between the forward direction and the backward direction of the flat plate. Cell transfer device. 2. The cell migration device according to claim 1, wherein a groove is formed on a side surface of the flat plate. 3. The cell migration device according to claim 1, further comprising a baffle member that blocks the flow of the solution at a position apart from the flat plate in the chamber.