JP2013240879A - Piezoelectric actuator, manipulator, manipulator system and operation method of fine object - Google Patents

Abstract

A piezoelectric actuator or the like that can obtain high responsiveness and can suppress vibrations other than the axial direction of a drive shaft.
In a piezoelectric actuator that finely drives a capillary 35 for manipulating a minute object by a piezoelectric element, a pipette holding member 34 having the capillary 35 attached and threaded on the outer periphery thereof, and the pipette holding member 34 are provided. A housing having a coaxial inner peripheral surface, at least two rolling bearings rotatably supporting the pipette holding member 34 with respect to the housing, a piezoelectric element disposed coaxially with the pipette holding member 34, and the housing A piezoelectric actuator comprising: a lid that is fixed to the inner ring and that fixes the piezoelectric element in an axial direction; and an inner ring spacer disposed between inner rings of the two rolling bearings.
[Selection] Figure 1

Description

  The present invention relates to a piezoelectric actuator, a manipulator, a manipulator system, and a method for operating a minute object that manipulate a minute object such as a cell.

  In the biotechnology field, a manipulator is known that operates on a minute object such as a cell such as injecting a sperm or DNA solution into an egg or cell under a microscope (see, for example, Patent Document 1). Patent Document 2 discloses a microscope apparatus that uses an electric manipulator having an operating needle to easily set the tip of an operating needle such as a glass capillary near the target position of the sample, and focuses the focus. Switch between interlocking and non-interlocking with the manipulator drive and drive the operating needle to set the operating needle.

  Patent Documents 3 and 4 describe a manipulator that applies a shock load to a glass capillary or the like using a piezoelectric actuator including a piezoelectric element to perforate an egg cell or the like in order to enable stable micro movement of the glass capillary or the like. Has been.

JP 2004-325836 A JP 2006-23487 A Japanese Patent Publication No. 06-98582 JP 2003-1574 A

  In the manipulator described in Patent Document 3, the piezoelectric actuator is fixed only to a pipette holding member to which a glass capillary or the like is attached, and is not fixed to the manipulator. In such a configuration, there is a possibility that the pipette holding member is dropped when the manipulator is driven. Further, in the manipulator disclosed in Patent Document 3, the pipette holding member is fixed by a contact member that holds a small portion of the entire pipette holding member with a frictional force. There was a problem that responsiveness was affected.

  In the manipulator described in Patent Document 4, the pipette holding member and the piezoelectric actuator are not arranged coaxially, and the axis of the pipette holding member and the axis of the piezoelectric actuator are in a twisted relationship. Further, the drive shaft of the piezoelectric actuator is separated from the pipette holding member. For this reason, the glass capillary tends to vibrate other than the axial direction of the drive shaft. Furthermore, since a preload is applied to the piezoelectric element by a tension spring, it is difficult to obtain high responsiveness in terms of preload adjustment.

  In view of the above, an object of the present invention is to provide a piezoelectric actuator, a manipulator, a manipulator system, and a method for operating a micro object having high responsiveness. Another object of the present invention is to provide a piezoelectric actuator, a manipulator, a manipulator system, and a method for operating a micro object that suppress vibrations other than the axial direction of the drive shaft of the piezoelectric actuator.

  In order to achieve the above object, a piezoelectric actuator according to the present invention is a piezoelectric actuator that finely drives a capillary for manipulating a minute object by a piezoelectric element, and is equipped with a pipette holding the capillary and threading the outer periphery. A member, a housing having an inner peripheral surface coaxial with the pipette holding member, at least two rolling bearings rotatably supporting the pipette holding member with respect to the housing, and a piezoelectric element arranged coaxially with the pipette holding member An element, a lid fixed to the housing and fixing the piezoelectric element in an axial direction, and an inner ring spacer disposed between inner rings of the two rolling bearings.

  Another piezoelectric actuator of the present invention is a piezoelectric actuator that finely drives a capillary for manipulating a minute object with a piezoelectric element, and a pipette holding member on which the capillary is mounted, and an inner circumference coaxial with the pipette holding member. A housing having a surface, at least two rolling bearings for supporting the pipette holding member with respect to the housing, a piezoelectric element disposed coaxially with the pipette holding member, and being fixed to the housing, the axial direction of the piezoelectric element And an inner ring spacer disposed between the inner rings of the two rolling bearings.

  Moreover, it is preferable to further provide a hollow member interposed between the inner ring of the two rolling bearings and the outer peripheral surface of the pipette holding member.

  Another piezoelectric actuator of the present invention is a piezoelectric actuator that finely drives a capillary for manipulating a minute object with a piezoelectric element, and a pipette holding member on which the capillary is mounted, and an inner circumference coaxial with the pipette holding member. A housing having a surface, at least two rolling bearings for supporting the pipette holding member with respect to the housing, a piezoelectric element disposed coaxially with the pipette holding member, and being fixed to the housing, the piezoelectric element being axially A lid to be fixed, an inner ring spacer disposed between inner rings of the two rolling bearings, a hollow member interposed between an inner ring of the two rolling bearings and an outer peripheral surface of the pipette holding member; It is characterized by providing.

  According to these structures, since the pipette holding member which is a drive shaft and the piezoelectric element are coaxially arranged, vibrations other than the axial direction of the drive shaft of the piezoelectric actuator can be suppressed.

  Further, it is preferable that the pipette holding member is threaded on the outer periphery, and the two rolling bearings are fixed in the axial direction by two lock nuts screwed with the outer periphery of the pipette holding member.

  Further, it is preferable that the outer peripheral surface of one end of the hollow member is threaded, and a lock nut is screwed into the threaded portion to fix the rolling bearing in the axial direction.

  Moreover, it is preferable to further include a fixing member provided at the other end of the hollow member and fixing the pipette holding member to the hollow member.

  Moreover, it is preferable that the piezoelectric element is preloaded by the rolling bearing. In this case, high responsiveness can be obtained by using a rolling bearing as a spring element having high rigidity.

  It is preferable that a spacer disposed coaxially with the pipette holding member is provided between the rolling bearing and the piezoelectric element.

  The capillary is preferably supported at a plurality of points by a plurality of support members.

  A manipulator according to the present invention includes the piezoelectric actuator described above.

  Further, another manipulator of the present invention includes a capillary for manipulating a minute object and the above-described piezoelectric actuator, and in the manipulator electrically driven by a controller, the capillary sucks or discharges the fluid in the capillary. It is connected to an injector, and the injector is set to reciprocate with a constant stroke by one operation signal generated from the controller.

  Further, another manipulator of the present invention includes a capillary for manipulating a minute object, and the manipulator is electrically driven by a controller, and the capillary is connected to an injector for sucking or discharging a fluid in the capillary, and the controller The injector is set so as to reciprocate with a constant stroke by one operation signal emitted from.

  In the reciprocation of the injector, it is preferable that the moving speed of the injector at the time of ejection is set larger than the moving speed of the injector at the time of suction of the fluid in the capillary.

  Further, in the reciprocation of the injector, it is preferable that the movement of the injector corresponding to the suction is performed first in the reciprocation of the injector by the operation signal.

  In addition, in the reciprocation of the injector, it is preferable that after the movement corresponding to the suction operation and the movement corresponding to the discharge operation are performed once, the injector stops before the next suction operation.

  The operation signal is preferably generated by a joystick connected to the controller.

  The operation signal is preferably generated by a button provided on the joystick.

  The manipulator system of the present invention is a controller that controls the voltage applied to the piezoelectric element according to the above-described manipulator that finely drives the capillary with a piezoelectric element, and the size of the tip of the capillary attached to the manipulator. And.

  A camera capable of imaging the tip of the capillary attached to the manipulator, and a measurement indicator disposed on an imaging screen imaged by the camera for measuring the size of the tip of the capillary; The controller further includes a voltage applied to the piezoelectric element within the standard range when the size of the tip of the capillary measured by the measurement indicator is equal to or greater than a preset standard range. When the capillary tip size measured by the measurement indicator is less than the standard range, the voltage applied to the piezoelectric element is set to the standard voltage. It is preferable to make it larger.

  The method for manipulating a micro object according to the present invention uses the above-described manipulator to perform zona pellucida perforation on the egg as the object with the capillary, and then the capillary moves to sample at least one sperm. It returns to the position of the zona pellucida after the operation, and the sperm injection operation is performed while moving the sperm in the capillary by the reciprocation of the injector.

  According to the piezoelectric actuator, the manipulator, the manipulator system, and the operation method of the minute object of the present invention, high responsiveness can be obtained. In addition, vibrations other than the axial direction of the drive shaft of the piezoelectric actuator can be suppressed.

FIG. 1 is a diagram schematically showing a configuration of a manipulator system according to the first embodiment. FIG. 2 is a cross-sectional view of a fine movement mechanism (piezoelectric actuator) that can be used in the manipulator system of FIG. FIG. 3 is a block diagram showing a main part of the control system by the controller of FIG. FIG. 4 is a diagram showing an example of a screen displayed on the display unit of FIG. FIG. 5 is a perspective view showing a specific example of the joystick shown in FIGS. 1 and 3. 6 is a diagram schematically showing relative positions (a) to (d) with respect to the bottom surface of the petri dish during operation of the injection capillary 35 of FIG. FIG. 7 is a diagram showing a change in the voltage value of the piezoelectric element when the capillary is in contact with the bottom surface of the petri dish as shown in FIG. FIG. 8 is a diagram illustrating an example of two screens displayed on the display unit of FIG. FIG. 9 is a cross-sectional view of a fine movement mechanism (piezoelectric actuator) that can be used in the manipulator system according to the second embodiment. FIG. 10 is a cross-sectional view showing a capillary fixing method. FIG. 11 is a perspective view of a fine movement mechanism (piezoelectric actuator) that can be used in the manipulator system according to the third embodiment. FIG. 12 is a cross-sectional view of a fine movement mechanism (piezoelectric actuator) that can be used in the manipulator system according to the third embodiment. FIG. 13 is a perspective view of a fine movement mechanism (piezoelectric actuator) according to a modification of the third embodiment. FIG. 14 is a cross-sectional view of a fine movement mechanism (piezoelectric actuator) according to a modification of the third embodiment. FIG. 15 is a diagram schematically showing a configuration of a manipulator system according to the fourth embodiment. FIG. 16 is a diagram schematically showing the configuration of the manipulator of FIG. FIG. 17 is a block diagram showing the main part of the control system by the controller of FIG. FIG. 18 is a perspective view showing a specific example of the joystick shown in FIG. FIG. 19 is a diagram showing the positional relationships (a) to (h) between the capillaries mounted on the manipulator and the minute operation objects (eggs, sperm). FIG. 20 is a diagram showing the states (a) to (d) after completion of sperm sampling in FIG. FIG. 21 is a diagram illustrating an example of the operation of the joystick and the change in the position of the injector relative to the operation. FIG. 22 is a diagram illustrating an example of the operation of the joystick and a change in the position of the injector relative thereto. FIG. 23 is a diagram illustrating an example of a screen displayed on the display unit of the manipulator system according to the fifth embodiment. FIG. 24 is a diagram illustrating an example of a screen displayed on the display unit of the manipulator system according to the fifth embodiment. FIG. 25 is a diagram illustrating an example of a screen displayed on the display unit of the manipulator system according to the fifth embodiment. FIG. 26 is a flowchart regarding control of the manipulator system according to the fifth embodiment.

  The best mode for carrying out the present invention will be described below with reference to the drawings. In addition, this invention is not limited by this embodiment. In addition, constituent elements in the following embodiments include those that can be easily replaced by those skilled in the art or those that are substantially the same.

[First Embodiment]
(Configuration of manipulator system)
FIG. 1 is a diagram schematically showing a configuration of a manipulator system according to the first embodiment. The manipulator system 10 is a system for performing an artificial operation on a sample (cell, egg, sperm, etc.) that is a minute object under a microscope. In FIG. 1, the manipulator system 10 includes a microscope unit 12, a manipulator 14, and a manipulator 16, and the manipulators 14 and 16 are separately arranged on both sides of the microscope unit 12. The manipulator system 10 includes a controller 43 that controls the microscope unit 12 and the pair of manipulators 14 and 16.

  The microscope unit 12 includes a camera 18 as an image sensor, a microscope 20, and a sample table, and a petri dish 22 is disposed on the sample table. The microscope unit 12 has a structure in which the microscope 20 is disposed immediately above the petri dish 22. That is, the microscope 20 is composed of an inverted microscope. Note that the microscope 20 and the camera 18 have an integrated structure, and although not shown, a microscope is provided with a light source that emits light toward the petri dish 22.

  For example, a solution containing a sample (not shown) is accommodated in the petri dish 22. In this state, when the sample in the petri dish 22 is irradiated with light from the microscope 20 and the light reflected by the sample in the petri dish 22 (for example, a cell or an egg) enters the microscope 20, an optical image related to the cell or egg is After being magnified at 20, the image is taken by the camera 18, and the sample can be observed based on the image taken by the camera 18.

(Configuration of manipulator)
As shown in FIG. 1, a manipulator 14 on one side (the left side in the drawing) includes a pipette 24, an XY axis table 26, a Z axis table 28, as a manipulator having an X axis-Y axis-Z axis orthogonal configuration. A driving device 30 for driving the XY axis table 26 and a driving device 32 for driving the Z axis table 28 are provided. A capillary 25 that is a capillary tip is attached to the tip of the pipette 24.

  The pipette 24 is connected to a Z-axis table 28, the Z-axis table 28 is arranged on the XY axis table 26 so as to be movable up and down, and the drive devices 30 and 32 are connected to a controller 43.

  The XY axis table 26 is configured to move along the X axis or the Y axis by driving the driving device 30, and the Z axis table 28 is moved along the Z axis (vertical) by driving the driving device 32. (Along the axial direction). The pipette 24 connected to the Z-axis table 28 moves in a three-dimensional space as a moving area according to the movement of the XY axis table 26 and the Z-axis table 28, and the sample (cells etc.) in the petri dish 22 is moved through the capillary 25. It is comprised so that it may be interposed. That is, the manipulator 16 is a holding manipulator used for holding a minute object.

  The manipulator 16 on the other side (the right side in the figure) includes a pipette (injection pipette) holding member 34, an XY axis table 36, a Z axis table 38, and an XY axis table 36 as an orthogonal three-axis manipulator. A driving device 40 for driving and a driving device 42 for driving the Z-axis table 38 are provided. The pipette holding member 34 is connected to a Z-axis table 38, the Z-axis table 38 is disposed on the XY axis table 36 so as to be movable up and down, and the driving devices 40 and 42 are connected to the controller 43. A glass capillary 35 is attached to the tip of the pipette holding member 34.

The XY axis table 36 is configured to move along the X axis or the Y axis by driving the driving device 40, and the Z axis table 38 is moved along the Z axis (vertical) by driving the driving device 42. (Along the axial direction). The pipette holding member 34 connected to the Z-axis table 38 moves as a moving area in the three-dimensional space according to the movement of the XY axis table 36 and the Z-axis table 38, and the sample in the petri dish 22 is passed through the capillary 35 and the like. And is configured to perform an artificial operation. In other words, the manipulator 16 is an injection manipulator that is used for manipulation (perforation, injection, sampling, etc.) of a minute object.
Thus, the manipulators 14 and 16 have substantially the same configuration, and the manipulator 16 to which the pipette holding member 34 is connected will be described below as an example.

  The XY axis table 36 is configured to move along the X axis or the Y axis by the drive (motor) of the drive device 40, and the Z axis table 38 is moved to the Z axis by the drive (motor) of the drive device 42. It is configured to move along the axis (along the vertical axis direction). In addition, the Z-axis table 38 is connected to a pipette holding member 34 for holding a capillary 35 into which cells and eggs in the petri dish 22 are to be inserted.

  That is, the XY axis table 36 and the Z axis table 38 are moved by driving the driving devices 40 and 42 using a three-dimensional space including cells in the petri dish 22 as a moving region. The XY axis table 36 and the Z axis table 38, for example, move the pipette holding member 34 from the tip end side of the pipette holding member 34 to the insertion position for inserting the capillary 35 into the sample in the petri dish 22. Coarse. The XY axis table 36 and the Z axis table 38 are configured as such a coarse movement mechanism (three-dimensional axis movement table).

  Further, the connecting portion between the Z-axis table 38 and the pipette holding member 34 has a function as a nanopositioner. The nanopositioner supports the pipette holding member 34 so as to be freely movable in the installation direction (longitudinal direction), and further finely drives the pipette holding member 34 along the longitudinal direction (axial direction). It is configured.

  Specifically, a connecting portion between the Z-axis table 38 and the pipette holding member 34 is provided with a fine movement mechanism 44 as a nanopositioner. Next, the fine movement mechanism 44 will be described with reference to FIG.

(Configuration of fine movement mechanism)
FIG. 2 is a cross-sectional view of a fine movement mechanism (piezoelectric actuator) that can be used in the manipulator system of FIG. As shown in FIG. 2, the fine movement mechanism 44 includes a piezoelectric actuator 44 a including a pipette holding member 34. The piezoelectric actuator 44a includes a housing 48 that constitutes a main body of the piezoelectric actuator 44a. A pipette holding member 34 whose outer periphery is threaded is inserted into a housing 48 whose inner periphery is formed in a cylindrical shape. The pipette holding member 34 has a capillary 35 attached and fixed to the tip side (the left side in FIG. 2, the same applies hereinafter), and the rear end side (the right side in FIG. A tube (not shown) for sending a solution (such as a culture solution) is connected. A flow rate adjusting pump is connected to the other end of the tube.

  The pipette holding member 34 is supported by the housing 48 via rolling bearings 80 and 82. The rolling bearings 80 and 82 include inner rings 80a and 82a, outer rings 80b and 82b, and balls 80c and 82c inserted between the inner rings 80a and 82a and the outer rings 80b and 82b, respectively. In the rolling bearings 80 and 82, the inner rings 80 a and 82 a are fitted to the outer peripheral surface of the pipette holding member 34 via the hollow member 84, and the outer rings 80 b and 82 b are fitted to the inner peripheral surface of the housing 48 to hold the pipette. The member 34 is rotatably supported.

  The inner rings 80 a and 82 a are fitted to the pipette holding member 34 via the hollow member 84. Thereby, it is possible to fit the outer peripheral surface of the pipette holding member 34 in which the inner rings 80a and 82a are threaded. Further, the attachment of the rolling bearings 80 and 82 to the pipette holding member 34 is simplified.

  Further, the hollow member 84 is provided with a flange portion 84a as an inner ring spacer projecting radially outward at a substantially central portion in the axial direction, and the inner rings 80a of the rolling bearings 80 and 82 are provided on both axial sides of the flange portion 84a. , 82a are arranged. At this time, the hollow member 84 and the flange portion 84a are integrated. Thereafter, lock nuts 86 and 86 are screwed into the pipette holding member 34 from the front end side of the inner ring 80a and the rear end side of the inner ring 82a, and the axial positions of the rolling bearings 80 and 82 are fixed. The axial dimension of the hollow member 84 is smaller than the sum of the axial dimension of the inner rings 80a and 82a of the rolling bearings 80 and 82 and the axial dimension of the flange portion 84a of the hollow member 84. For this reason, the axial front end side of the inner ring 80 a and the axial rear end side of the inner ring 82 a protrude in the axial direction from the hollow member 84. As a result, the inner rings 80a and 82a are directly fixed in the axial direction by the lock nuts 86 and 86, so that the axial movement of the inner rings 80a and 82a can be restricted.

  In the first embodiment, by providing the hollow member 84, the inner diameters of the pipette holding member 34 and the rolling bearings 80 and 82 used may not be the same. On the other hand, in the case of the same diameter, a configuration in which the hollow member 84 is omitted may be used. Moreover, although the hollow member 84 and the flange part 84a were comprised integrally, you may make it a different body. Further, the integrated hollow member 84 and flange portion 84a may be handled as an inner ring spacer.

  Furthermore, an annular spacer 90 that is arranged coaxially with the rolling bearings 80 and 82 and fits with the inner peripheral surface of the housing 48 with a positive gap is arranged on the rear end side in the axial direction of the outer ring 82b. An annular piezoelectric element 92 is disposed substantially coaxially with the spacer 90 on the rear end side in the axial direction of the spacer 90, and a lid 88 of the housing 48 is disposed on the rear end side in the axial direction. The lid 88 is for fixing the piezoelectric element 92 in the axial direction, and has a hole through which the pipette holding member 34 is inserted. The lid 88 is fastened to the side surface of the housing 48 with a bolt (not shown). The lid 88 may be fixed by screwing the inner peripheral surface on the rear end side in the axial direction of the housing 48 and the outer peripheral surface of the lid 88 and screwing them together. May occur. For this reason, it is preferable that the lid 88 is fastened and fixed by a bolt or the like.

  The rolling bearings 80 and 82 and the piezoelectric element 92 are preloaded by adjusting the length of the spacer 90 and tightening the lid 88. Specifically, when the length of the spacer 90 is adjusted and the lid 88 is closed, the fastening force corresponding to the position is applied to the outer ring 82b of the rolling bearing 82 and the outer ring 80b of the rolling bearing 80 along the axial direction. As well as a preload is applied to the piezoelectric element 92 at the same time. Thus, a predetermined preload is applied to the rolling bearings 80 and 82 and the piezoelectric element 92, and a gap 94 is formed as a distance between the axial directions between the outer rings 80b and 82b of the rolling bearings 80 and 82.

  Thus, since the preload can be applied by the rolling bearings 80 and 82 which are highly rigid spring elements, it is possible to easily adjust the preload to the piezoelectric element 92 and to achieve high responsiveness.

  Further, since the piezoelectric element 92 is in contact with the rolling bearing 82 via the spacer 90, a piezoelectric element having a special shape such as a piezoelectric element having the same diameter as the outer ring 82b or a piezoelectric element having a dimension capable of applying a predetermined preload is used. There is no need to use it. That is, in the example of FIG. 2, the annular piezoelectric elements 92 may be arranged in a rod shape or prismatic shape so as to be substantially even in the circumferential direction of the spacer 90, and have a hole portion through which the pipette holding member 34 is inserted. A square tube may be used. Further, if the shape of the spacer 90 is made highly accurate, the inner peripheral surface of the housing 48 is formed with an accuracy that can be fitted to the rolling bearings 80 and 82. The rolling bearing 82 can be pressed evenly. In the following, “the piezoelectric element is (substantially) coaxial” does not only indicate that the center axis is shared with an axis having an annular piezoelectric element, but is centered on an axis with a piezoelectric element. This includes the case where they are arranged equally on the circumference and the case where a certain axis passes through the center of a piezoelectric element of a rectangular tube.

  The piezoelectric element 92 is connected to a controller 43 as a control circuit via a lead wire (not shown), and expands and contracts along the longitudinal direction (axial direction) of the pipette holding member 34 according to the voltage from the controller 43. It is constituted as one element of the piezoelectric actuator. That is, the piezoelectric element 92 expands and contracts along the axial direction of the pipette holding member 34 in response to the applied voltage from the controller 43, and finely moves the pipette holding member 34 along the axial direction. When the pipette holding member 34 finely moves along the axial direction, this fine movement is transmitted to the capillary 35, and the position of the capillary 35 is finely adjusted.

  As the voltage waveform of the voltage applied to the piezoelectric element 92, a sine wave, a rectangular wave, a triangular wave, or the like can be used. In addition, as a method of applying a voltage to the piezoelectric element 92, a signal waveform is continuously output while an operator presses a button (for example, a button 43B of a joystick 47 (FIG. 5) described later) connected to the controller 43. May be driven, or a burst waveform may be used.

  In the first embodiment, of the rolling bearings 80 and 82, the displacement amount of the inner ring 80 a and the outer ring 80 b of the rolling bearing 80, and half of the expansion / contraction amount (displacement amount) of the piezoelectric element 92 is set as the displacement amount of the capillary 35. Therefore, a fine movement voltage obtained by adding a control voltage for giving a displacement twice the fine movement displacement amount and an initial setting voltage is applied to the piezoelectric element 92.

  For example, when 2 × elongation occurs in the piezoelectric element 92, the pressing force due to the elongation presses the outer ring 82b of the rolling bearing 82 in addition to the preload before performing fine movement control, and the outer ring 80b of the rolling bearing 80 is axially moved. The gap 94 between the outer rings 80b, 82b of the rolling bearings 80, 82 is further narrowed by 2x to absorb the extension of the piezoelectric element 92 in the axial direction.

  The displacement of the gap 94 is caused by the displacement of the rolling bearings 80 and 82 by x in the axial direction along with the elastic deformation, and the displacement of the outer ring 80b of the rolling bearing 80 by 2x in accordance with the axial direction.

  Conversely, when the piezoelectric element 92 contracts by 2x, the pressing force decreases, the elastic deformation of the rolling bearings 80 and 82 decreases by x, and the outer ring 80b of the rolling bearing 80 is aligned with the axial direction so that the gap 94 is widened. Therefore, the displacement of the piezoelectric element 92 is absorbed.

  In this way, since the rolling bearings 80 and 82 absorb the displacement x of the gap 94 separately for each x, the inner rings 80a and 80b of the rolling bearings 80 and 82 are balanced when the forces pressing the rolling bearings 80 and 82 are balanced. Is displaced together with the pipette holding member 34 in the axial direction. For example, at the time of an injection operation in which an egg is perforated and injected with sperm, half of the expansion / contraction amount 2x of the piezoelectric element 92 becomes a fine displacement amount of the capillary 35, and the capillary 35 is positioned at the insertion position. After the capillary 35 is positioned at the insertion position, when an injection voltage is applied to the piezoelectric element 92, the capillary 35 performs an injection operation.

  According to the above-described configuration, since the capillary 35 and the piezoelectric element 92 are coaxially arranged, excessive vibration, that is, vibration generated in a direction other than the axial direction of the pipette holding member 34 is reduced when the piezoelectric element 92 is driven. can do. Further, since the piezoelectric actuator 44a of FIG. 2 is directly fixed to the manipulator 16 and the pipette holding member 34, parts for fixing to the manipulator 16 and the pipette holding member 34 are unnecessary. For this reason, it is possible to improve the assemblability and reduce the cost by reducing the number of parts. Furthermore, since the piezoelectric actuator 44a and the pipette holding member are directly fixed, the distance between the piezoelectric element 92 and the capillary 35 can be shortened. As a result, during the injection operation, a more accurate drilling operation can be performed, and the punching action by the piezoelectric element 92 can be improved.

  The fine movement mechanism 44 described above is provided in the manipulator 16 for cell manipulation, but may be provided in the manipulator 14 for cell holding, or may be omitted.

(Manipulator system control)
Next, control by the controller 43 of the manipulator system 10 will be described with reference to FIGS. FIG. 3 is a block diagram showing a main part of the control system by the controller of FIG. FIG. 4 is a diagram showing an example of a screen displayed on the display unit of FIG. FIG. 5 is a perspective view showing a specific example of the joystick shown in FIGS. 1 and 3.

  The controller 43 in FIGS. 1 and 3 includes a CPU (Central Processing Unit) as a calculation means and hardware resources such as a hard disk, a RAM, and a ROM as storage means, and performs various calculations based on a predetermined program. The drive command is output so as to perform various controls according to the calculation result. That is, the controller 43 controls the driving devices 30 and 32 of the manipulator 14, the driving devices 40 and 42 of the manipulator 16, the piezoelectric element 92 of the fine movement mechanism 44, and the like via a driver or an amplifier provided as necessary. A drive command is output to each. For example, the piezoelectric element 92 is driven by a voltage signal generated from a signal generator 95 controlled by the controller 43 and amplified by an amplifier 96.

  The controller 43 is connected with a joystick 47, a mouse 43A, and a button 43B (FIG. 1) in addition to a keyboard as information input means, and is further connected with a display unit 45 comprising a CRT or a liquid crystal panel. In 45, a microscope image acquired by the camera 18, various control screens, and the like are displayed.

  The controller 43 automatically drives the manipulators 14 and 16 in a predetermined sequence. Such sequence driving is performed by the controller 43 sequentially outputting a drive command to each based on the calculation result of the CPU by a predetermined program.

  For the operation of the manipulator system 10 in FIG. 1, a joystick 47 connected to the controller 43 can be mainly used as shown in FIGS. 1, 3, and 5, and one manipulator 14 and 16 is prepared. . The joystick 47 has a plurality of buttons 47a to 47g and a handle 47h as shown in FIG. The handle 47h is tilted (tilted) in the right direction R and the left direction L to drive the drive devices 30 and 40 in FIG. 1, and the manipulators 14 and 16 can be driven in the X axis direction and the Y axis direction to rotate (twist). Thus, the driving devices 32 and 42 can be driven to drive in the Z-axis direction. Further, the operation of each function can be assigned to each of the buttons 47a to 47g. For example, the operation of the piezoelectric element 92 of the piezoelectric actuator 44a (fine movement mechanism 44) in FIG.

  In the above configuration, when the injection manipulator 16 is driven, the handle 47h of the joystick 47 is operated to drive the XY axis table 36 and the Z axis table 38 coarsely, and the pipette holding member 34 is moved into the petri dish 22. After positioning near the cell, the pipette holding member 34 can be finely driven using the fine movement mechanism 44.

  Specifically, when the glass capillary 35 is attached to the pipette holding member 34, the manipulators 14 and 16 are driven so that the pipette holding member 34 is retracted from the petri dish 22 disposed at the microscope work site. To do. Thereby, when the capillary 35 is attached to the pipette holding member 34, a sufficient working space is obtained.

  After the capillary 35 is attached to the pipette holding member 34, the manipulator 14 is driven by a command from the controller 43 based on the operation of the joystick 47 and the like, and the pipette holding member 34 to which the capillary 35 is attached is moved to the petri dish that is a microscope work location. Move toward 22.

  When the capillary 35 is moved to the microscope work location, in the first (first) operation, the switching button 45c in FIG. 4 is operated to reduce the microscope field magnification of the image displayed on the image display unit 45a. By driving the driving devices 40 and 42 and the fine movement mechanism 44 of the manipulator 16, the driving of the driving devices 40 and 42 and the fine movement mechanism 44 is stopped as soon as the capillary 35 can be confirmed in the field of view of the microscope 20.

  Thereafter, by using the image processing of the controller 43 and driving the driving devices 40 and 42 and the fine movement mechanism 44, the capillary 35 is moved to the optimum position within the field of view of the microscope 20, and the driving devices 40 and 42 and the fine movement mechanism 44 are moved. The drive of the mechanism 44 is stopped. At this time, the movement amount by the tables 36 and 38 and the fine movement mechanism 44 driven in the first operation is stored in the controller 43. In order to move the capillary to the optimum position, either or both of the XYZ driving system (XY axis table 36, Z axis table 38) and fine movement mechanism 44 by the driving devices 40 and 42 are used as appropriate.

  Next, when the manipulator 16 is operated and the petri dish 22 or the capillary 35 needs to be replaced, the driving devices 40 and 42 and the fine movement mechanism 44 are driven to retract the capillary 35 from the microscope work site. I do. At this time, the capillary 35 is driven to the set position by operating the joystick 47. In addition, you may make it retract to arbitrary positions using the button 43B.

  On the other hand, when the capillary 35 is moved again to the microscope work place, the controller 43 stores the position when it is set for the first time, so that the position of the capillary 35 can be easily adjusted by the manipulator 16. Become.

  When the capillary 35 having a uniform shape is used, the efficiency can be improved as compared with the conventional one by using the manipulator 16 according to the first embodiment. Even when the shape of the capillary 35 varies, the pipette holding member 34 can be linearly reciprocated by driving the piezoelectric actuator 44a, so that the position of the capillary 35 can be finely adjusted.

  Further, when the capillary 35 is positioned at the cell insertion position, the injection operation by the pipette holding member 34 is performed by operating the joystick 47 to apply the injection voltage to the piezoelectric element 92 and finely driving the fine movement mechanism 44. It can be performed. At this time, since the preload is applied to the piezoelectric element 92 by the rolling bearings 80 and 82 which are highly rigid spring elements, high responsiveness can be achieved.

  FIGS. 6 and 7 show the operation when the capillary 35 for injection is moved and set to the optimum position before the injection operation. FIG. 6 is a diagram schematically showing relative positions (a) to (d) with respect to the bottom surface of the petri dish during operation of the injection capillary of FIG. FIG. 7 is a diagram showing a change in the voltage value of the piezoelectric element when the capillary is in contact with the bottom surface of the petri dish as shown in FIG.

[Second Embodiment]
Next, a manipulator system 120 according to the second embodiment will be described with reference to FIGS. 9 and 10. In the second embodiment, only parts different from the first embodiment will be described in order to avoid the description overlapping with the first embodiment. In the second embodiment, the fine movement mechanism 144 (piezoelectric actuator 144a) is partially different from the fine movement mechanism 44 (piezoelectric actuator 44a) of the first embodiment. FIG. 9 is a cross-sectional view of a fine movement mechanism (piezoelectric actuator) that can be used in the manipulator system according to the second embodiment.

  In the fine movement mechanism 144 of the second embodiment, since the hollow member 135 is provided on the outer periphery of the pipette holding member 134 and the hollow member 135 is integrated with the piezoelectric actuator 144a, the pipette holding member 134 and the piezoelectric actuator 144a are separated separately. Can be handled. 9, parts equivalent to those in FIG. 2 are denoted by the same reference numerals, and detailed description thereof is omitted.

  The pipette holding member 134 has the capillary 35 attached and fixed to the tip side (the left side in FIG. 9, the same applies hereinafter). In addition, a nozzle for connecting a tube (not shown) for sending a solution for injection into an egg, a cell, or the like is fixed to the rear end side (the right side of FIG. 9, the same applies hereinafter) by screwing or the like. . A flow rate adjusting pump is connected to the other end of the tube. Next, the piezoelectric actuator 144a attached to the pipette holding member 134 will be described.

  Rolling bearings 80 and 82 are fitted to the outer peripheral surface of the hollow member 135 that forms the central axis of the piezoelectric actuator 144a. The inner ring 80 a of the rolling bearing 80 is positioned by contacting an abutting surface 135 b formed on the outer peripheral surface of the hollow member 135. An inner ring spacer 184 is provided between the inner rings 80 a and 82 a of the rolling bearings 80 and 82. The inner ring spacer 184 is fitted to the outer peripheral surface of the hollow member 135. The rolling bearings 80 and 82 (inner rings 80a and 82a) are fixed in the axial direction by screwing a lock nut 86 into the hollow member 135 from the rear end side of the inner ring 82a.

  Other parts of the piezoelectric actuator 144a are the same as those in FIG. That is, the housing 48 is fitted to the outer peripheral surfaces of the outer rings 80b and 82b of the rolling bearings 80 and 82 as in FIG. A spacer 90 and a piezoelectric element 92 are disposed in this order on the inner peripheral surface of the housing 48 on the rear end side in the axial direction of the outer ring 82b, and these are fixed by tightening the lid 88. In this way, the piezoelectric actuator 144a integrated with the hollow member 135 is configured.

  In order to fix the pipette holding member 134 to the piezoelectric actuator 144 a, the hollow member 135 is fitted and fixed to the outer peripheral surface of the pipette holding member 134. A part of the outer peripheral surface of the pipette holding member 134 is enlarged to be provided with a stepped portion 134a. The hollow member 135 is provided with a stepped portion 135a corresponding to the stepped portion 134a on the inner diameter side, and is positioned in the axial direction by making both face each other. The hollow member 135 positioned in the axial direction is fixed to the pipette holding member 134 by a set screw (not shown). More specifically, a plurality of screw holes (not shown) penetrating in the radial direction are provided in a protruding portion 135c protruding in the axial direction from the housing 48 in the axial front end portion (left side in FIG. 9) of the hollow member 135. ing. A plurality of set screws (not shown) are screwed into the plurality of screw holes and brought into contact with the pipette holding member 134. Thereby, the pipette holding member 134 is fixed.

  By configuring the fine movement mechanism 144 as described above, the pipette holding member 134 and the piezoelectric actuator 144a can be separated. As a result, the maintainability of the fine movement mechanism 144 can be improved. Further, since the hollow member 135 is fixed with a set screw, the coaxiality and relative position between the hollow member 135 and the pipette holding member 134 can be finely adjusted. Since such a set screw is provided on the projecting portion 135c of the hollow member 135, it is easy to attach and remove the set screw, so that the maintainability of the fine movement mechanism 144 can be further improved.

  In the case of the fine movement mechanism 44 shown in FIG. 2, since it is necessary to perform a wide range of screw processing from the front end to the rear end of the pipette holding member 34, the pipette holding member 34 may be deformed. On the other hand, in the fine movement mechanism 144 of FIG. 3, it is not necessary to thread the pipette holding member 134. For this reason, deformation due to processing of the pipette holding member 134 and the hollow member 135 can be suppressed.

  In the above example, the hollow member 135 and the pipette holding member 134 are fixed by a set screw. However, the present invention is not limited to this, and adhesive fixing, press-fit fixing, and screwing fixing may be used. In the above example, the axial positioning is performed by the step portions 134a and 135a. However, the present invention is not limited to this, and the axial position may be determined only by the set screw without providing the step portions 134a and 135a. A configuration may be adopted in which the approximate position is indicated by a marker. Furthermore, in the above-described example, after the piezoelectric actuator 144a is assembled, the hollow member 135 and the pipette holding member 134 that form a part of the piezoelectric actuator 144a are fitted and fixed, but the present invention is not limited to this. That is, after the hollow member 135 is fitted and fixed to the pipette holding member 134, other components of the piezoelectric actuator 144a may be assembled, and the above-described effects are not based on the assembling procedure. However, when assembling property is considered, it is preferable to fix the hollow member 135 and the pipette holding member 134 after assembling the piezoelectric actuator 144a.

Other configurations and operational effects are the same as those of the fine movement mechanism 44 of FIG.
Next, a method for fixing the capillary 35 to the tip of the fine movement mechanisms 44 and 144 of the first and second embodiments shown in FIGS. 2 and 9 will be described with reference to FIG. FIG. 10 is a cross-sectional view showing a capillary fixing method.

  As shown in FIG. 10, an enlarged diameter portion 34a for inserting the capillary 35 is formed at the tip of the pipette holding member 34 (134, hereinafter the same). The inner diameter of the enlarged diameter portion 34 a is set larger than the outer diameter of the capillary 35. On the outer periphery of the tip of the pipette holding member 34, a holding member 136 having an arrow-shaped cross section and a hollow inside on the inner diameter side is fitted. The rear end side of the capillary 35 is enclosed in the enlarged member 34 a of the holding member 136 and the pipette holding member 34.

  The inner peripheral surface of the holding member 136 includes a small diameter portion 136a on the front end side and a large diameter portion 136b on the rear end side. The small diameter portion 136 a has an inner diameter slightly larger than the outer diameter of the capillary 35. When the capillary 35 is fixed, the small diameter portion 136a guides the capillary 35 to a rough position where the capillary 35 is fixed in the radial direction. The large diameter portion 136 b has an inner diameter slightly larger than the outer peripheral surface of the pipette holding member 34. The inner peripheral surface of the large-diameter portion 136b supports the capillary 35 via two sets of support members 130. The support member 130 includes two O-rings 138 and two washers 137 that sandwich the O-ring 138. The support members 130 are disposed at two positions on the outer peripheral surface of the capillary 35 (the inner peripheral surface of the large diameter portion 136b) separated in the axial direction, and the spacer 141 is disposed therebetween. The front end side of the outer peripheral surface of the holding member 136 has a tapered shape that gradually decreases in diameter from the rear end side to the front end side. Thereby, for example, when the piezoelectric actuator 44a (144a) is operated, the petri dish 22 and the holding member 136 are difficult to contact. The rear end side of the outer peripheral surface of the holding member 136 is male threaded.

  A cylindrical nut member 139 is attached to the rear end side of the holding member 136. The inner peripheral surface of the front end side of the nut member 139 is internally threaded so as to be screwed with the external thread of the holding member 136. Further, a reduced diameter portion 139a is provided on the rear end side of the nut member 139. The inner diameter of the reduced diameter portion 139 a is slightly larger than the pipette holding member 34. The pipette holding member 34 is provided with a circumferential groove, and a retaining ring 140 is fitted into the circumferential groove. The end surface on the distal end side of the reduced diameter portion 139a abuts against the retaining ring 140 and is prevented from coming off. Another example of the retaining ring 140 is a protrusion that is integral with the pipette holding member 34. In this case, the nut member 139 is inserted from the rear end side of the pipette holding member 34 before the pipette holding member 34 is assembled to the piezoelectric actuator 44a (144a).

  The capillary 35 is supported and fixed by the holding member 136 and the nut member 139. The procedure for attaching the capillary 35 is as follows. First, the capillary 35 is inserted through the holding member 136 in which the support member 130 and the spacer 141 are assembled. In this state, the capillary 35 is supported in the radial direction only by the O-ring 138 constituting the two sets of support members 130. On the other hand, after attaching the nut member 139 to the pipette holding member 34, the retaining ring 140 is attached to the pipette holding member 34. Thereafter, the support member 130 on the rear end side of the holding member 136 and the tip of the pipette holding member 34 are brought into contact with each other. In this state, the nut member 139 and the holding member 136 are screwed together. Thereby, a force contracting in the radial direction acts on the threaded portion of the holding member 136, and the O-ring 138 of the support member 130 on the rear end side is deformed so as to be crushed in the radial direction. Thereby, the capillary 35 is fixed in the axial direction and the radial direction, and the support and fixing of the capillary 35 is completed. Further, the airtightness at the connecting portion between the pipette holding member 34 and the capillary 35 can be ensured by screwing the holding member 136 and the nut member 139. For this reason, the flow rate of the liquid in the capillary 35 can be adjusted with the above-described flow rate adjusting pump connected to the pipette holding member 34.

  Conventionally, a configuration in which a capillary is supported by only one support member using an O-ring is used (for example, “Eppendorf Microinjector FemtoJet (registered trademark) express usage manual”). In such a configuration, since the capillary is supported only at one location, for example, when the egg cell is perforated, an unexpected vibration occurs in the capillary due to the driving of the piezoelectric actuator, and the cell is damaged or the efficiency is lowered. there is a possibility. On the other hand, according to the configuration shown in FIG. 10, two support members 130 each having an O-ring 138 are used and the capillary 35 is supported at two points, so that the capillary is being driven while the piezoelectric actuators 44a and 144a are being driven. It is suppressed that 35 moves. As a result, the vibration of the capillary 35 during cell operation can be reduced, and the perforation performance / efficiency can be improved as compared with the conventional case.

  In the above-described configuration, two support members 130 are used. However, the present invention is not limited to this, and three or more support members 130 may be used. Furthermore, the number of O-rings 138 constituting one support member 130 is not limited to two, but may be one or more, and the washer 137 may be omitted. In addition, the constituent members of the support member 130 are not limited to the washer 137 and the O-ring 138, and any configuration that can support the capillary 35 can be applied.

[Third Embodiment]
Next, with reference to FIG.11 and FIG.12, the manipulator system 200 which concerns on 3rd Embodiment is demonstrated. Note that in the third embodiment, only parts different from the second embodiment will be described in order to avoid descriptions overlapping with the second embodiment. In the second embodiment, the pipette holding member 134 is fixed to the hollow member 135 with a set screw. However, in the third embodiment, the pipette holding member 234 is fixed to the hollow member 235 using another fixing member instead of the set screw. doing. FIG. 11 is a perspective view of a fine movement mechanism (piezoelectric actuator) that can be used in the manipulator system according to the third embodiment. FIG. 12 is a cross-sectional view of a fine movement mechanism (piezoelectric actuator) that can be used in the manipulator system according to the third embodiment.

  In the fine movement mechanism 244 of the third embodiment, since the hollow member 235 is provided on the outer periphery of the pipette holding member 234 and the hollow member 235 is integrated with the piezoelectric actuator 244a, the pipette holding member 234 and the piezoelectric actuator 244a are separated. It is possible. 12, parts equivalent to those in FIG. 9 are denoted by the same reference numerals, and detailed description thereof is omitted.

  The pipette holding member 234 has a capillary 35 attached and fixed to the tip side (the left side in FIG. 12, the same applies hereinafter). In addition, a nozzle for connecting a tube (not shown) for sending a solution for injection into an egg, a cell, or the like is fixed to the rear end side (the right side in FIG. 12, the same applies hereinafter) by screwing or the like. . A flow rate adjusting pump is connected to the other end of the tube. Next, the piezoelectric actuator 244a attached to the pipette holding member 234 will be described.

  Rolling bearings 80 and 82 are fitted to the outer peripheral surface of the hollow member 235 that forms the central axis of the piezoelectric actuator 244a. The hollow member 235 has a projecting portion 235a projecting radially outward on the tip side of the inner ring 80a (the left side in FIG. 12, the same applies hereinafter), and the projecting portion 235a comes into contact with the lock nut 236. A surface 235b is formed. The inner ring 80 a of the rolling bearing 80 is positioned by contacting a lock nut 236 provided on the outer peripheral surface of the hollow member 235.

  An inner ring spacer 184 is provided between the inner rings 80 a and 82 a of the rolling bearings 80 and 82. The inner ring spacer 184 is fitted to the outer peripheral surface of the hollow member 235. The rolling bearings 80 and 82 (inner rings 80a and 82a) are fixed in the axial direction by screwing a lock nut 237 into the hollow member 235 from the rear end side of the inner ring 82a.

  Other parts of the piezoelectric actuator 144a are the same as those in FIG. That is, the housing 48 is fitted to the outer peripheral surfaces of the outer rings 80b and 82b of the rolling bearings 80 and 82, as in FIG. A spacer 90 and a piezoelectric element 92 are disposed in this order on the inner peripheral surface of the housing 48 on the rear end side in the axial direction of the outer ring 82b, and these are fixed by tightening the lid 88. Thus, the piezoelectric actuator 144a integrated with the hollow member 235 is configured.

  In order to fix the pipette holding member 234 to the piezoelectric actuator 244a, a clamping 240 as a fixing member is provided on the distal end side of the hollow member 235. The hollow member 234 and the clamping 240 are provided integrally. The clamping 240 has a C-shaped cross section in which both end faces are opposed to each other with a predetermined gap. The clamping 240 has a fastening screw 241, and the fastening screw 241 is fastened and moved in a direction in which both end surfaces approach each other, thereby narrowing an inner peripheral surface through which the pipette holding member 234 is inserted. On the other hand, the clamping 240 widens the inner peripheral surface through which the pipette holding member 234 is inserted by loosening the fastening screw 241 and moving the both end surfaces away from each other. Thereby, the pipette holding member 234 inserted into the hollow member 235 is held on the inner peripheral surface of the clamping 240 by tightening the fastening screw 241 of the clamping 240 connected to the hollow member 235, and the clamp 240 And fixed to the hollow member 235.

  By configuring the fine movement mechanism 244 as described above, the pipette holding member 234 and the piezoelectric actuator 244a can be separated. As a result, the maintainability of the fine movement mechanism 244 can be improved. Further, since the pipette holding member 234 is fixed to the hollow member 235 by the clamping 240, the coaxiality and relative position between the hollow member 235 and the pipette holding member 234 can be finely adjusted. In addition, the piezoelectric actuator 244a can be fixed at a predetermined position in the axial direction of the pipette holding member 234. Therefore, the piezoelectric actuator 244a can be fixed to the pipette holding member 234 so that the capillary 35 and the piezoelectric element 92 are close to each other. As described above, by making the capillary 35 and the piezoelectric element 92 close to each other, the perforating action by the piezoelectric element 92 can be further improved.

  Further, even in the fine movement mechanism 244 of the third embodiment, since it is not necessary to thread the pipette holding member 234, deformation due to the processing of the pipette holding member 234 and the hollow member 235 can be suppressed. Other configurations and operational effects are the same as those of the fine movement mechanism 144 of FIG.

  In the third embodiment, the C-shaped clamping is used as the clamping 240. However, the present invention is not limited to this configuration. For example, the clamping according to the modification shown in FIGS. 13 and 14 may be used. Good. Here, a clamping 250 according to a modification will be described with reference to FIGS. 13 and 14. FIG. 13 is a perspective view of a fine movement mechanism (piezoelectric actuator) according to a modification of the third embodiment. FIG. 14 is a cross-sectional view of a fine movement mechanism (piezoelectric actuator) according to a modification of the third embodiment.

  The clamping 250 as a fixing member provided on the distal end side of the hollow member 235 is a coupling type clamping in which an annular shape is divided into two. That is, the clamping 250 includes one split member 250a, the other split member 250b, and two fastening screws 251 that fasten the split members 250a and 250b. One division member 250a is provided integrally with the hollow member 234, and the other division member 250b is provided so as to be movable in the contact / separation direction with respect to the one division member 250a. A pipette holding member 234 is disposed between one split member 250a and the other split member 250b. When the two fastening screws 251 are tightened, the clamping 250 moves in a direction in which the other divided member 250b approaches the one divided member 250a, thereby sandwiching the pipette holding member 234. On the other hand, when the two fastening screws 251 are loosened, the clamping 250 moves in the direction in which the other divided member 250b is opened with respect to the one divided member 250a, thereby opening the pipette holding member 234. As a result, the pipette holding member 234 inserted into the hollow member 235 is held by the clamping 250 when the fastening screw 251 of the clamping 250 connected to the hollow member 235 is tightened, and the hollow member 235 is interposed via the clamping 250. Fixed to.

  Even with such a clamping 250, the pipette holding member 234 and the piezoelectric actuator 244a can be separated as described above. As a result, the maintainability of the fine movement mechanism 244 can be improved. Further, since the pipette holding member 234 is fixed to the hollow member 235 by the clamping 250, the coaxiality and relative position between the hollow member 235 and the pipette holding member 234 can be finely adjusted. In addition, the piezoelectric actuator 244a can be fixed at a predetermined position in the axial direction of the pipette holding member 234. Therefore, the piezoelectric actuator 244a can be fixed to the pipette holding member 234 so that the capillary 35 and the piezoelectric element 92 are close to each other. As described above, by making the capillary 35 and the piezoelectric element 92 close to each other, the perforating action by the piezoelectric element 92 can be further improved.

[Fourth Embodiment]
Next, a manipulator system 300 according to the fourth embodiment will be described with reference to FIGS. 15 to 21. In the fourth embodiment, the operation of the manipulator in the manipulator systems 1, 120, and 200 according to the first to third embodiments will be described in detail. In the fourth embodiment, description will be made by applying to the first embodiment, and only different parts from the first embodiment will be described. FIG. 15 is a diagram schematically showing a configuration of a manipulator system according to the fourth embodiment.

  A manipulator system 300 according to the fourth embodiment includes the pair of manipulators 14 and 16, the sample stage 321, a microscope unit 325, a light source unit 326, and a controller 343 for controlling them.

  The microscope unit 325 includes a microscope 322 that includes an objective lens 322a and the like and has a microscope function, a camera 323 as an imaging device, and a focusing mechanism 324 capable of automatic focusing operation. The microscope 322 is composed of an inverted microscope positioned below the petri dish 22 in which the objective lens 322a accommodates a sample that is an observation object. The focusing mechanism 324 may be configured to automatically perform a focusing operation, or may be configured to perform a focusing operation in advance or based on focal position information stored during work.

  The sample stage 321 includes a petri dish 22 made of a translucent material such as a glass material, and is configured of an XY axis table so that it can be electrically driven in the plane direction of the XY axes, and a driving device 321a. It can be moved along the X axis by driving (FIG. 17) and along the Y axis by driving the driving device 321b (FIG. 17).

  The light source unit 326 is arranged so as to be positioned immediately above the petri dish 22 on the sample stage 321 and irradiates light toward the sample in the petri dish 22.

  When light from the light source unit 326 is irradiated on the sample in the petri dish 22 on the sample stage 321 and the light transmitted through the sample in the petri dish 22 is incident on the microscope 322, an optical image related to the minute object is enlarged by the microscope 322 to a predetermined magnification. Then, the image is picked up by the camera 323, and the sample can be observed based on the image picked up by the camera 323. At this time, the sample or micro object in the petri dish 22 can be set at a position suitable for observation by driving the sample stage 321 in the plane direction of the XY axes.

(Configuration of manipulator)
FIG. 16 is a diagram schematically showing the configuration of the manipulator of FIG.
As shown in FIG. 16, the manipulator 14 has a configuration substantially similar to that of the first embodiment, and thus a part of the description is omitted. A tube (not shown) for connecting the syringe pump 329 (FIG. 17) and the pipette 24 is attached to the end of the pipette 24 opposite to the capillary 25.

  The pipette 24 is connected to a Z-axis table 28, the Z-axis table 28 is arranged on the XY axis table 26 so as to be movable up and down, and drive devices 30 and 32 are controllers (personal computers (PCs in FIG. 4)). 343. The pipette 24 is configured to move in the three-dimensional space as a moving area in accordance with the movement of the XY axis table 26 and the Z axis table 28, and to hold minute objects (cells, eggs, sperm, etc.) in the petri dish 22. Has been.

  Since the manipulator 16 has substantially the same configuration as that of the first embodiment, a part of the description is omitted. A pipe (not shown) for connecting the infusion pump 339 (FIG. 17) and the pipette 34 is attached to the end of the pipette holding member 34 opposite to the capillary 35.

The pipette holding member 34 is connected to a Z-axis table 38, the Z-axis table 38 is disposed on the XY axis table 36 so as to be movable up and down, and the driving devices 40 and 42 are connected to the controller 43. The pipette holding member 34 moves in the three-dimensional space as a moving region in accordance with the movement of the XY axis table 36 and the Z axis table 38, and operates the capillary 35 by operating the injection pump 339 and the piezoelectric element 92. Thus, an artificial operation is performed on the sample in the petri dish 22 or the minute object (cell, egg, sperm, etc.) in the sample.
Thus, the holding manipulator 14 and the injection manipulator 16 have substantially the same configuration. The detailed configurations of the fine movement mechanisms 44, 144, 244, etc. of the manipulators 14, 16 are the configurations shown in the first to third embodiments.

(Manipulator system control)
Next, control by the controller (personal computer (PC)) 343 in the manipulator system 300 will be described with reference to FIG. FIG. 17 is a block diagram showing the main part of the control system by the controller of FIG.

  The controller 343 shown in FIG. 17 includes a CPU (Central Processing Unit) as a calculation unit and hardware resources such as a hard disk, a RAM, and a ROM as a storage unit, performs various calculations based on a predetermined program, and performs calculation results. Accordingly, the control unit 346 outputs a drive command so as to perform various controls. That is, the control unit 346 includes the focusing mechanism 324 of the microscope unit 325 in FIG. 15, the driving devices 30 and 32 of the manipulator 14, the syringe pump 329, the driving devices 40 and 42 of the manipulator 16, the injection pump 339, and the fine movement mechanism 44. The piezoelectric element 92 is controlled, and a drive command is output to each via a driver, an amplifier, or the like provided as necessary.

  The controller 343 is connected with a joystick 347, a mouse 349, a button (not shown), a tablet (not shown), etc. in addition to a keyboard as information input means, and a display unit 345 including a CRT or a liquid crystal panel. Are connected, and the display unit 345 displays a microscope image acquired by the camera 323 and various control screens.

  In addition, the control unit 346 automatically drives the manipulators 14 and 16 in a predetermined sequence. Such sequence driving is performed by the control unit 346 sequentially outputting a driving command to each based on the calculation result of the CPU by a predetermined program. For example, when operating a plurality of eggs in the petri dish 22, the manipulator 14 , 16 performs an operation for distinguishing between an operated egg and an unoperated egg.

  The controller 343 includes an image input unit 382 that receives an image signal of a microscope field of view captured by the camera 323 through the microscope 322, an image processing unit 383 that performs image processing of the image signal from the image input unit 382, and before and after image processing. The image output unit 384 for outputting the image information to the display unit 345, the position of the nucleus of the operation object imaged by the camera 123, the positions of the capillaries 25 and 35, and the like as the image information after the image processing. And a position detection unit 385 for detecting based on the control unit 346. The units 382 to 385 are controlled by the control unit 346.

  For example, the image processing unit 383 performs edge extraction processing and pattern matching to detect the position of the detection target, and the position detection unit 385 detects the positions of the micro target and the capillaries 25 and 35 based on the processing results. Then, the driving of the capillaries 25, 35, etc. is controlled based on those detection positions or their detection position information and the position information set in advance or set during work.

  In addition, the display unit 345 displays a microscopic image of the minute object including the images of the capillaries 25 and 35 captured by the camera 323, information on the calculation result, and the like.

  The controller 343 controls the drive of the drive devices 321a and 321b of the sample stage 321 by operating a joystick 347 and the like connected to the controller 343, and moves the sample stage 321 in the XY axis direction. Further, the controller 343 controls the sample stage 321 by operating a joystick 347 connected to the controller 343 and drives the manipulators 14 and 16 to set the capillaries 25 and 35 at predetermined positions. The drive amounts of the drive devices 321a, 321b, 30, 32, 49, 42 and the piezoelectric actuators 44a, 144a, 244a (piezoelectric element 92) driven during the operation are stored. Alternatively, the movement amounts of the X, Y, and Z axes of the sample stage 321 and the manipulators 14 and 16 are stored. At this time, the driving amount, the moving amount, or the moved position may be stored as X and Y coordinates from a predetermined reference position. For example, the controller 343 stores the second positions of the capillaries 25 and 35 so that after the capillaries 25 and 35 move to the first position or the third position away from the second position, the joystick 347 or the like It can be returned to the second position by an operation instruction.

  Each position of the capillaries 25 and 35 is a relative position with respect to a specific position in the petri dish 22, and the sample stage 321 moves the petri dish 22 placed on the petri dish 22 in the plane direction of the XY axes so that the capillaries 25 and 35 are moved. Move relatively between each position.

  Moreover, the sample stage 321 may include a position sensor 321c configured by an encoder or the like that detects each position in the X-axis direction and the Y-axis direction of the XY-axis table, as indicated by a broken line in FIG. The controller 343 stores XY coordinate information obtained by detecting the respective positions of the capillaries 25 and 35 by the position sensor 321c, and the sample stage 321 controls the capillaries 25 and 35 by the control of the controller 343 based on the XY coordinate information. Move to the first position, the second position, and the third position.

  The manipulator system 300 according to the fourth embodiment drives the manipulators 14 and 16 and the sample stage 321 mounted on the microscope 322 by operating the joystick 347 and the like while confirming an image from the camera 323 with the display unit 345 of the controller 343.

  When performing the injection operation by the manipulator system 300, the sample stage 321 is driven in a state where the petri dish 22 is set on the sample stage 321, and the operation of storing the position information of the other medium in the controller 343 is performed. This position storage operation can be performed even during the injection operation, and the storage position can be changed each time.

(Joystick configuration and operation example)
Next, a joystick 347 as an operation means connected to the controller of FIG. 17 and an example of the operation will be described with reference to FIG. FIG. 18 is a perspective view showing a specific example of the joystick shown in FIG. Note that the joystick 347 in FIG. 18 corresponds to the configuration of the manipulator system 300, and is partially different from the joystick 47 in FIG.

  The operations of the microscope unit 325 and the manipulators 14 and 16 in FIGS. 15 and 17 are controlled by the control unit 346 in FIG. 17 based on input information by operating the joystick 347. In the fourth embodiment, an example in which one joystick 347 is prepared for each of the holding manipulator 14 and the injection manipulator 16 will be described. However, the microscope unit 325 and the manipulators 14 and 16 are operated by one joystick. It is also possible to operate with three or more joysticks, or to use a mouse 349, keyboard, tablet, etc. (hereinafter referred to as the operation unit including the joystick 347) connected to the controller 343. May be.

  As shown in FIG. 18, the joystick 347 stands upright from the base and is gripped by the operator and tilted to the right R and left L, and can be operated to be twisted. The first, second and third push button switches 347a, 347b, 347c arranged side by side on the upper side, the multi-directional hat switch 347d arranged in the upper part, such as four directions and eight directions, and the push button A trigger switch 347g disposed on the opposite side of the switches 347a to 347c and a lever 347h are provided.

  The push button switches 347a to 347c, the multi-directional hat switch 347d, the main body 347e, the trigger switch 347g, and the lever 347h of the joystick 347 in FIG. -Y-axis tables 26 and 36, Z-axis tables 28 and 38 drive devices 30, 32, 40 and 42, syringe pump 329, injection pump 339 pusher (not shown, hereinafter referred to as injector), piezoelectric element 92, sample Operation functions for driving each of the driving devices 321a and 321b of the stage 321 are assigned. For example, by tilting the main body 347e to the right R and left L while pulling the trigger switch 347g, the XY driving of the manipulators 14 and 16 can be performed, and the Z driving can be performed by twisting the main body 347e. To.

  Further, with respect to the holding manipulator 14, when the upper and lower buttons of the multi-directional hat switch 347d are pressed, the focusing mechanism 324 is driven and the microscope 322 can be focused, and when the right and left buttons are pressed. XY plane rotation and YZ plane rotation with respect to an operation target such as an egg can be performed, and the push button switches 347b and 347c are for driving adjustment of the syringe pump 329, and the push button switches 347b and 347c When one is pressed, the suction pressure (negative pressure) of the holding capillary 25 by the syringe pump 329 can be adjusted. Further, for example, the sequence driving can be automatically performed on the manipulators 14 and 16 by using the push button switch 347a. In addition, the controller 343 can store position information of each part related to the focusing of the microscope 322 as a movement amount or coordinates.

  In addition, regarding the injection manipulator 16, fine movement in the XY plane driven by a motor can be controlled using a multi-directional hat switch 347d, and the push button switches 347b and 347c respectively perform suction and discharge operations of an injection pump 339 (pressor (injector)). The push button switch 347a is for turning on and off the reciprocating motion of the injector.

  The lever 347h rotates in the direction A in the figure and in the opposite direction B, and can be switched to an upper end position rotated in the direction A, a lower end position rotated in the direction B, and an intermediate position thereof. The changeover switch of the lever 347h corresponds to the amplitude of the reciprocating motion of the injector. The switching of the lever 347h is not limited to three steps, and may be two steps, four steps or more, and no step.

  The manipulator 14 is driven by the operation of the push button switch or the like in the joystick 347 of FIG. 18, the capillary 25 holds the minute object (eg egg) on the petri dish 22, and the holding suction pressure (negative pressure) ) Is controlled.

  In addition, the piezoelectric actuators 44a, 144a, and 244a of the manipulator 16 are driven by the operation of the push button switch and the like on the joystick 347, and the tip of the capillary 35 is linearly displaced in the injection direction, so that a minute object (eg, egg) A predetermined solution (such as a suspension culture solution containing sperm) is injected into a minute object (eg, egg) from the capillary 35 inserted into the container by driving the injector. Further, if necessary, a voltage for perforation is applied to the piezoelectric element 92 during or after the drive of the capillary 35, the piezoelectric element 92 is driven, and the capillary 35 approaches or contacts the minute object. The egg is perforated by moving a minute amount, and the predetermined solution is injected (injected) into the minute object by driving the injector from the inserted capillary 35. Thereafter, the capillary 35 is driven so as to be pulled out from the position in the minute object. When the capillary 35 is clogged or there is a concern that clogging may occur, the push button switch 347a is pressed to reciprocate the injector and periodically suck and discharge the solution in the capillary 35. Can be made.

(Manipulator operation)
Next, an example of the operation of the above-described manipulator system 300 will be described with reference to FIGS. 19 and 20. FIG. 19 is a diagram showing the positional relationships (a) to (h) between the capillaries mounted on the manipulator and the minute operation objects (eggs, sperm). FIG. 19 shows a state in which the injection capillary 35 approaches the egg D held by the hold capillary 25 (a), a state in which the capillary 35 perforates the zona pellucida T of the egg D (b), and a capillary after puncture of the zona pellucida State (c) where 35 is removed from egg D, state (d) changed to sperm sampling mode, state (e) where capillary 35 is operated to sample sperm U, state where sampling of sperm U is completed ( f). 19 (e) and 19 (f) in which the sample stage 321 is not driven, FIGS. 19 (g) and 19 (h) respectively show the case where the sample stage 321 is driven during sampling of the sperm U. The state (g) which moved the sperm U to the position which is easy to sample, and the state (h) which completed the sampling after the movement are shown.

  FIG. 20 is a diagram showing the states (a) to (d) after completion of sperm sampling in FIG. FIG. 20 shows a state in which the capillary 35 is returned to the zona pellucida punching position after the sampling of the sperm U in FIG. 19 is changed to the injection mode (a), and the capillary 35 is inserted into the cytoplasm S of the egg D from the zona pellucida piercing position. It is a figure which shows the state (d) which pulled the capillary 35 from the state (b) which was rare, the state (c) which injected the sperm U into cytoplasm S, and the egg D.

  First, as shown in FIG. 19A, the hold side manipulator 14 is operated using a joystick 347, and the egg D is held by the capillary 25 with a negative pressure. In addition, the position shown by the thick line in FIG. 19A is the Z-axis (vertical) position where the focus is achieved, and the same applies to the following figures.

  Next, as shown in FIG. 19B, the manipulator 16 is operated using the joystick 347, the capillary 35 is moved to the injection position, and the piezoelectric element 92 of FIG. After that, the capillary 35 is once extracted from the egg D as shown in FIG. At this time, a perforated hole T1 is formed in the zona pellucida T of the egg D.

  Next, the controller 343 is operated by the operation unit to change to the sperm sampling mode and start the sperm sampling operation as shown in FIG. 19 (d). At this time, the position of the focusing mechanism 324, the injection side The controller 343 stores the XYZ axis positions of the hold side manipulators 14 and 16 and the XY axis position of the sample stage 321. This storage is executed, for example, by operating the joystick 347 in FIG.

  Thereafter, as shown in FIG. 19D, the focusing mechanism 324 and the Z axis of the manipulator 16 are automatically driven to a position where the microscope 322 is focused on the sperm U. Since the height from the bottom surface 22a of the petri dish 22 to the zona pellucida punching position (the position of the hole T1) is approximately constant, the position calculated from the position where the egg D is in focus by the controller 343 can be used. .

  Next, as shown in FIG. 19E, the sperm U is sampled by operating the capillary 35 by the movement of the injection-side manipulator 16 in the XYZ axial directions. Then, as shown in FIG. 19F, the sperm sampling is completed by holding the sperm U to be sampled in the vicinity of the tip of the capillary 35.

  Further, when sampling the sperm, as shown in FIG. 19 (g), the sample stage 321 is driven and the hold side manipulator 14 is also driven to move in the XY-axis direction by the same amount of movement in synchronism therewith. good. In this case, after the sample stage 321 and the manipulator 14 are moved, the sampling operation is performed to complete the sampling of the sperm U (FIG. 19 (h)).

  Next, after sampling the sperm U and holding it in the capillary 35 as described above, the controller 343 is operated with the joystick 347 to change to the sperm injection mode as shown in FIG. Then, by operating the controller 343 and automatically driving the injection side manipulator 16 in the XYZ axis directions, the capillary 35 returns to the zona piercing position stored in FIG. 19D, and at the same time, the focusing mechanism 324 is also stored. Drive to the specified position.

  At this time, if the sample stage 321 is also driven as shown in FIG. 19G, the hold side manipulator 14 and the sample stage 321 are moved to the previously stored positions. Thus, during the sperm sampling operation, the XY axes of the sample stage 321 and the hold side manipulator 14 are synchronously driven with the same movement amount, and therefore, after the sperm sampling, when the capillary 35 returns to the zona pellucida punching position, It is possible to prevent the hole T1 from being displaced.

  Next, as shown in FIG. 20B, the piezoelectric element 92 is driven to puncture the cell membrane from the hole T1 pierced by the capillary 35, and the capillary 35 is inserted into the cytoplasm S. Next, the sperm U is injected (injected) into the cytoplasm S from the capillary 35 as shown in FIG. Next, the capillary 35 is pulled out from the egg D as shown in FIG.

  From the state of FIG. 20B to the state of FIG. 20C, the injector is reciprocated by pressing the push button 347a of the joystick 347 as described above. Thus, by sucking and discharging the solution in the capillary 35, the sperm U can be moved in the capillary as shown by the arrow in FIG. As a result, the sperm U can be easily prevented and eliminated from being caught in the capillary. In the case of a conventional manipulator, such an operation can be performed only by pressing the push buttons 347b and 347c alternately. In order to prevent and eliminate the catch of the sperm U, skill of the operator is required. On the other hand, since the injector can be reciprocated with a single button, even an unskilled person can easily prevent and eliminate the catch of the sperm U.

  Further, the stroke (amplitude) of the reciprocating motion of the injector can be changed by changing the position of the lever 347h of the joystick 347. On the other hand, the time interval T (reciprocating cycle) of the reciprocating motion is set in advance. In addition, the moving speed of the injector during the reciprocating motion is higher than that when the sperm U is injected (injected) into the egg D, that is, when the injector is discharged by the push button 347b (or 347c). It is preferable to set so.

  FIG. 21 is a diagram illustrating an example of the relationship between the operation of the joystick and the change in the injector position corresponding thereto. FIG. 21A is a graph showing the position of the lever 347h (stroke size) and the injector position information by turning the button 347a on and off, and FIG. 21B shows the change in the position of the sperm U corresponding to the change in the position of the injector. FIG.

  In this example, first, the lever 347h is operated to set a small amplitude (stroke) of the injector, and the push button 347a is pressed. As a result, the injector moves to the suction side (downward in FIG. 21A) and then moves to the discharge side (upward in FIG. 21A). As long as the button 347a is pressed, this suction / discharge operation (reciprocating motion of the injector) continues. When the time for pressing the button 347a is shorter than the preset time interval T, the injector only performs the suction operation and the discharge operation once in succession.

  In the second operation of the push button 347a in FIG. 21A, the position of the lever 347h is changed to set the magnitude of the amplitude to a large value, and the push button 347a longer than the preset time interval T is pushed. Thereby, the suction / discharge operation is repeated. As shown in the figure, the preset time interval T is the time during which the injector is at a position during the first suction operation (or discharge operation) and the injector at the same position during the second suction operation (or discharge operation). It is the difference from a certain time. For this reason, the reciprocation of the injector is not always continuous, and after the suction operation and the discharge operation are performed once, the injector may stop before the next suction operation. Of course, the suction / discharge operation may be repeated continuously.

  In the third operation of the push button 347a in FIG. 21A, the position of the lever 347h is changed to set the magnitude of the amplitude small, and the time push button 347a shorter than the preset time interval is pushed. As a result, the suction / discharge operation is continuously performed once.

  FIG. 21B shows the position of the sperm U in the capillary 35 corresponding to the third operation of the push button 347a. Circle numbers 1 to 3 in the figure correspond to circle numbers 1 to 3 in FIG. As shown in FIG. 21A, the movement speed of the injector during the reciprocating motion is higher during ejection than during suction (the inclination of the graph of the injector position information is larger). For this reason, as shown in FIG. 21B, even if suction and discharge are repeated with the same amplitude, the amount of movement of sperm during discharge becomes larger than that during suction. As a result, it is possible to inject (inject) into the cytoplasm S of the egg D while repeating suction and discharge to prevent sperm from being caught.

  The operation of the injector is not limited to that described above. For example, as shown in FIG. 22, it may be combined with a relatively gentle suction / discharge operation by the push buttons 47b and 47c. FIG. 22 is a diagram illustrating an example of the operation of the joystick and a change in the position of the injector relative thereto. Alternatively, suction / discharge operation, that is, any one of the amplitude of the reciprocating motion of the injector, the time interval, the moving speed of the injector, or a combination thereof may be numerically input to the controller 343. The order of suction / discharge operation may be reversed from the example. Further, all the operations of the injector may be set in advance, and the injector may be operated by pressing the push button 347a. The injector operation, the magnitude of the injection voltage applied to the piezoelectric element 92, the application timing, etc. Alternatively, the setting may be made in advance in association with the operation of the injector.

[Fifth Embodiment]
Next, a manipulator system 400 according to the fifth embodiment will be described with reference to FIGS. In the fifth embodiment, the applied voltage to be applied to the piezoelectric element 92 is set according to the thickness of the capillary 35 of the injection-side manipulator 16 used in the first to fourth embodiments. This is because the driving condition of the piezoelectric element 92 is the same depending on the thickness of the tip of the capillary 35 or the state of consumables such as various samples used (for example, the medium in the petri dish 22). This is because the piercing action may be different. In this case, a slight difference in perforation may affect the sample after the injection operation. In the fifth embodiment, description will be made by applying to the first embodiment, and only different parts from the first embodiment will be described. 23 to 25 are diagrams illustrating examples of screens displayed on the display unit of the manipulator system according to the fifth embodiment.

  The screen displayed on the display unit 45 of the fifth embodiment, that is, the screen imaged by the camera 18 is for measurement for measuring the thickness (size) of the capillary 35 in addition to the capillary 35 of the injection-side manipulator 16. An indicator 410 is displayed. That is, the display information regarding the measurement indicator 410 is stored in the controller 43, and the controller 43 displays the measurement indicator 410 on the screen of the display unit 45 based on the stored display information.

  The measurement indicator 410 is formed in a rectangular shape on the screen, and has a second region E2 that is an outer region and a first region E1 that is an inner region. The second region E2 has the same length as the first region E1 in the long side direction, and is longer than the first region E1 in the short side direction. The first region E1 is provided at the center of the second region E2 in the short side direction. The first region E1 is formed shorter than the second region E2 in the short side direction.

  The first region E1 is a region for determining whether the thickness of the capillary 35 is equal to or less than the standard range. That is, when the thickness of the capillary 35 is equal to or smaller than the length in the short side direction of the first region E1, the capillary 35 is determined to be equal to or smaller than the standard range. The second region E2 is a region for determining whether or not the thickness of the capillary 35 is equal to or greater than the standard range. That is, when the thickness of the capillary 35 is not less than the length in the short side direction of the second region E2, the capillary 3 is determined to be not less than the standard range. When the thickness of the capillary 35 is larger than the length of the first region E1 in the short side direction and smaller than the length of the second region E2 in the short side direction, the capillary 35 is within the standard range. Determined.

  The measurement indicator 410 is not limited to the above configuration as long as the thickness of the tip of the capillary 35 can be measured. For example, the measurement indicator 410 may be an object with a scale.

  The thickness of the capillary 35 is measured by overlapping the capillary 35 on the measurement indicator 410. When the measurement indicator 410 and the capillary 35 are overlapped, they are overlapped so that the long side direction of the measurement indicator 410 and the axial direction of the capillary 35 coincide. Further, the measurement indicator 410 is overlaid so that the center in the short side direction coincides with the axial center of the capillary 35.

  When the measurement indicator 410 and the capillary 35 are overlapped, the capillary 35 may be appropriately moved by the XY axis table 36 and overlapped with the measurement indicator 410. Alternatively, when the measurement indicator 410 and the capillary 35 are overlapped, the controller 43 may change the display position of the measurement indicator 410 so that the measurement indicator 410 is appropriately moved to overlap the capillary 35. Good.

  The controller 43 superimposes the measurement indicator 410 and the capillary 35, and determines the thickness of the capillary 35 by performing image processing on the superimposed screen. Specifically, as shown in FIG. 23, when the capillary 35 is within the first region E1 as a result of superimposing the measurement indicator 410 and the capillary 35, the controller 43 determines that the length of the outer diameter of the capillary 35 is The capillary 35 is determined to be equal to or smaller than the standard range, assuming that it is equal to or shorter than the length in the short side direction of the first region E1.

  As shown in FIG. 24, when the measurement indicator 410 and the capillary 35 are overlapped and the capillary 35 is larger than the first region E1 and fits in the second region E2, the controller 43 is connected to the outside of the capillary 35. The capillary 35 is determined to be within the standard range assuming that the length of the diameter is longer than the length of the first region E1 in the short side direction and shorter than the length of the second region E2 in the short side direction.

  Further, as shown in FIG. 25, when the measurement indicator 410 and the capillary 35 are overlapped and the capillary 35 is larger than the second region E2, the controller 43 determines that the length of the outer diameter of the capillary 35 is the first. It is determined that the capillary 35 is not less than the standard range, assuming that it is not less than the length in the short side direction of the two regions E2.

  Then, the controller 43 appropriately sets the applied voltage to be applied to the piezoelectric element 92 according to the thickness of the capillary 35 determined using the measurement indicator 410. Specifically, when the capillary 35 is within the standard range, the controller 43 applies a standard applied voltage (hereinafter referred to as a standard (applied) voltage) to the piezoelectric element 92 to drive the fine movement mechanism 44. Further, when the capillary 35 is below the standard range, the controller 43 applies an applied voltage larger than the standard applied voltage to the piezoelectric element 92 to drive the fine movement mechanism 44. At this time, the controller 43 sets the applied voltage higher than the standard applied voltage by multiplying the standard applied voltage by the first gain larger than 1. Furthermore, when the capillary 35 is not less than the standard range, the controller 43 applies an applied voltage smaller than the standard applied voltage to the piezoelectric element 92 to drive the fine movement mechanism 44. At this time, the controller 43 sets the applied voltage smaller than the standard applied voltage by multiplying the standard applied voltage by the second gain smaller than 1.

  Next, with reference to FIG. 26, the control of the controller 43 relating to the setting of the applied voltage applied to the piezoelectric element 92 will be described. FIG. 26 is a flowchart related to the control of the manipulator system 400 according to the fifth embodiment. The applied voltage is set before the sperm U is injected (injected) into the egg D.

  First, the controller 43 performs image processing on the screen (for example, FIGS. 23 to 25) of the display unit 45 where the measurement indicator 410 and the capillary 35 overlap each other, and determines whether or not the capillary 35 is below the standard range. (Step S1). When the controller 43 determines that the capillary 35 is below the standard range (step S1: Yes), the controller 43 sets an applied voltage obtained by multiplying the standard applied voltage by the first gain (step S2), and performs processing related to setting of the applied voltage. finish. Then, the controller 43 drives the fine movement mechanism 44 by applying the set applied voltage to the piezoelectric element 92. At this time, since the applied voltage applied to the piezoelectric element 92 is larger than the standard applied voltage, the expansion of the piezoelectric element 92 is larger than when the standard applied voltage is applied. Thereby, the controller 43 can increase the amount of operation of the capillary 35 by the fine movement mechanism 44.

  If controller 43 determines in step S1 that capillary 35 is not below the standard range (step S1: No), controller 43 determines whether capillary 35 is above the standard range (step S3). When the controller 43 determines that the capillary 35 is not less than the standard range (step S3: Yes), the controller 43 sets an applied voltage obtained by multiplying the standard applied voltage by the second gain (step S4), and performs processing related to setting of the applied voltage. finish. At this time, since the applied voltage applied to the piezoelectric element 92 is smaller than the standard applied voltage, the expansion of the piezoelectric element 92 is smaller than when the standard applied voltage is applied. Thereby, the controller 43 can reduce the amount of operation of the capillary 35 by the fine movement mechanism 44.

  If the controller 43 determines in step S3 that the capillary 35 is not above the standard range (step S3: No), the controller 43 sets the standard applied voltage assuming that the capillary 35 is within the standard range (step S5). At this time, since the applied voltage applied to the piezoelectric element 92 is a standard applied voltage, the piezoelectric element 92 has a standard extension that is set in advance, and the amount of operation of the capillary 35 by the fine movement mechanism 44 is small. Standard operating amount.

  As described above, according to the fifth embodiment, it is possible to appropriately set the driving condition of the fine movement mechanism 44 according to the thickness of the capillary 35 and change the operation amount of the capillary 35 by the fine movement mechanism 44 to an optimum one. . For this reason, in the manipulator system 400, the injection operation of the sperm U with respect to the egg D can be made with a sufficient precision.

  In the fifth embodiment, the voltage applied to the piezoelectric element 92 is set after measuring the thickness of the tip of the capillary 35 using the measurement indicator 410. However, when the thickness of the tip of the capillary 35 is known in advance, the applied voltage to be applied to the piezoelectric element 92 may be set without measuring the tip of the capillary 35 by the measurement indicator 410. That is, when the thickness of the tip of the capillary 35 is known in advance, information on the thickness of the capillary 35 is input to the controller 43. Then, the controller 43 determines whether the capillary 35 is equal to or larger than the standard range, equal to or smaller than the standard range, or within the standard range based on the input information on the thickness of the capillary 35.

  Further, the manipulator systems 1, 120, 200, 300, and 400 according to the first to fifth embodiments may be combined with each other.

In the above embodiment, although the manipulator for injection was demonstrated, the use of this invention is not limited to this.
In other words, in order to collect a sample attached to the petri dish, it may be applied to a manipulator (for example, Japanese Patent Application Laid-Open No. 2008-229776) for applying vibration to the capillary.
In this case, by making the distance between the capillary and the piezoelectric actuator wider than in the case of the above-described embodiment, when the vibration is applied from the piezoelectric actuator, the capillary swings with the law of inertia (the motion dullness with respect to the vibration). The sample can be peeled from the base.

  According to the present invention, the injection operation and the sample peeling operation as described above can be performed by a piezoelectric actuator having a simple configuration with a small number of parts that does not require a linear motion device such as a ball screw or a motor. In addition, since the outer periphery of the pipette holding member is threaded and each part is attached with a corresponding female screw, it is easier to attach compared to the case where each part is attached by press fitting, and the capillary (pipette holding member tip Side) and the piezoelectric actuator can be easily finely adjusted.

  Further, according to the present invention, it is possible to easily prevent the nucleus to be injected from sticking to and getting caught in the capillary without requiring skill. For this reason, the operator can concentrate on the capillary positioning operation, and can realize a more accurate operation.

  In the above description, the present invention has been described only for the case where sperm is injected into an egg, but it can also be applied to the case where ES cells are injected. In particular, when a plurality of cells must be held in the capillary for injection, when the held cells are aligned in the capillary, the injector is driven to reciprocate as described above. The cells can be rocked and aligned.

  The present invention may be appropriately combined with other inventions. Examples of other inventions include, for example, JP2009-208220, JP2009-2111030, JP2009-211027, and JP2010-148460. And JP-A-2011-013416.

DESCRIPTION OF SYMBOLS 10 Manipulator system 14 Manipulator 16 Manipulator 18 Camera 22 Petri dish 24 Pipette 25 Capillary 26 XY axis table 28 Z axis table 30 Drive device 32 Drive device 34 Pipette holding member 35 Capillary 36 XY axis table 38 Z axis table 40 Drive device 42 Drive unit 43 Controller 44 Fine movement mechanism 44a Piezoelectric actuator 45 Display unit 47 Joystick 48 Housing 80, 82 Rolling bearing 80a, 82a Inner ring 80b, 82b Outer ring 80c, 82c Ball 84 Hollow member 84a Flange unit 86 Lock nut 88 Lid 90 Spacer 92 Piezoelectric Element 94 Gap 120 Manipulator system (second embodiment)
130 Support Member 134 Pipette Holding Member (Second Embodiment)
135 Hollow member 136 Holding member 137 Washer 138 O-ring 139 Nut member 140 Retaining ring 141 Spacer 144 Fine movement mechanism (second embodiment)
144a Piezoelectric Actuator (Second Embodiment)
184 Inner ring spacer (second embodiment)
200 Manipulator System (Third Embodiment)
234 Pipette holding member (third embodiment)
235 Hollow member (third embodiment)
236 Lock nut 237 Lock nut 240 Clamping 241 Fastening screw 244 Fine movement mechanism (third embodiment)
244a Piezoelectric actuator (third embodiment)
250a Division member 250b Division member 251 Fastening screw Manipulator system 300 (4th Embodiment)
321 Sample stage 322 Microscope 323 Camera 324 Focusing mechanism 325 Microscope unit 326 Light source unit 329 Syringe pump 339 Injection pump 343 Controller (fourth embodiment)
345 Display unit 346 Control unit 347 Joystick 382 Image input unit 383 Image processing unit 384 Image output unit 385 Position detection unit 400 Manipulator system (fifth embodiment)
410 Indicator for Measurement E1 First Area E2 Second Area D Egg U Sperm

Claims (21)

In a piezoelectric actuator that finely drives a capillary for manipulating a minute object with a piezoelectric element,
A pipette holding member fitted with the capillary and threaded on the outer periphery;
A housing having an inner peripheral surface coaxial with the pipette holding member;
At least two rolling bearings rotatably supporting the pipette holding member with respect to the housing;
A piezoelectric element disposed coaxially with the pipette holding member;
A lid fixed to the housing and fixing the piezoelectric element in an axial direction;
An inner ring spacer disposed between the inner rings of the two rolling bearings. In a piezoelectric actuator that finely drives a capillary for manipulating a minute object with a piezoelectric element,
A pipette holding member equipped with the capillary;
A housing having an inner peripheral surface coaxial with the pipette holding member;
At least two rolling bearings for supporting the pipette holding member with respect to the housing;
A piezoelectric element disposed coaxially with the pipette holding member;
A lid fixed to the housing and fixing the piezoelectric element in an axial direction;
An inner ring spacer disposed between the inner rings of the two rolling bearings.   The piezoelectric actuator according to claim 1, further comprising a hollow member interposed between an inner ring of the two rolling bearings and an outer peripheral surface of the pipette holding member. In a piezoelectric actuator that finely drives a capillary for manipulating a minute object with a piezoelectric element,
A pipette holding member equipped with the capillary;
A housing having an inner peripheral surface coaxial with the pipette holding member;
At least two rolling bearings for supporting the pipette holding member with respect to the housing;
A piezoelectric element disposed coaxially with the pipette holding member;
A lid fixed to the housing and fixing the piezoelectric element in the axial direction;
An inner ring spacer disposed between the inner rings of the two rolling bearings;
A piezoelectric actuator comprising: a hollow member interposed between an inner ring of the two rolling bearings and an outer peripheral surface of the pipette holding member. The pipette holding member is threaded on the outer periphery,
5. The piezoelectric actuator according to claim 1, wherein the two rolling bearings are fixed in an axial direction by two lock nuts screwed to an outer periphery of the pipette holding member.   The outer peripheral surface of one end of the hollow member is threaded, and a lock nut is screwed into the threaded portion to fix the rolling bearing in the axial direction. The piezoelectric actuator as described.   5. The piezoelectric actuator according to claim 3, further comprising a fixing member provided at the other end of the hollow member and fixing the pipette holding member to the hollow member.   The piezoelectric actuator according to any one of claims 1 to 7, wherein the piezoelectric element is preloaded by the rolling bearing.   The piezoelectric actuator according to any one of claims 1 to 8, further comprising a spacer disposed coaxially with the pipette holding member between the rolling bearing and the piezoelectric element.   The piezoelectric actuator according to any one of claims 1 to 9, wherein the capillary is supported at a plurality of points by a plurality of support members.   A manipulator comprising the piezoelectric actuator according to any one of claims 1 to 10. A manipulator comprising a capillary for manipulating a minute object and the piezoelectric actuator according to any one of claims 1 to 10, and electrically driven by a controller,
The capillary is connected to an injector that sucks or discharges the fluid in the capillary,
A manipulator characterized in that the injector is set to reciprocate with a constant stroke by one operation signal generated from the controller. In a manipulator equipped with a capillary for manipulating a minute object and electrically driven by a controller,
The capillary is connected to an injector that sucks or discharges the fluid in the capillary,
A manipulator characterized in that the injector is set to reciprocate with a constant stroke by one operation signal generated from the controller.   14. The reciprocation of the injector, wherein the movement speed of the injector at the time of discharge is set larger than the movement speed of the injector at the time of suction of the fluid in the capillary. manipulator.   The manipulator according to any one of claims 12 to 14, wherein in the reciprocation of the injector, the reciprocation of the injector according to the operation signal is performed first in accordance with the suction.   16. The injector according to any one of claims 12 to 15, wherein in the reciprocation of the injector, after the movement corresponding to the suction operation and the movement corresponding to the discharge operation are performed once, the injector stops before the next suction operation. The manipulator according to item.   The manipulator according to any one of claims 12 to 16, wherein the operation signal is generated by a joystick connected to the controller.   The manipulator according to any one of claims 12 to 17, wherein the operation signal is generated by a button provided on the joystick. The manipulator according to any one of claims 11 to 18, wherein the capillary is finely driven by a piezoelectric element.
And a controller for controlling a voltage applied to the piezoelectric element in accordance with a size of a tip of the capillary attached to the manipulator. A camera capable of imaging the tip of the capillary attached to the manipulator;
A measurement indicator arranged on an imaging screen imaged by the camera and for measuring the size of the tip of the capillary;
The controller is
When the size of the tip of the capillary measured by the measurement indicator is equal to or larger than a preset standard range, the voltage applied to the piezoelectric element is a standard voltage applied when the size is within the standard range. Smaller than
The voltage applied to the piezoelectric element is made larger than the standard voltage when the size of the tip of the capillary measured by the measurement indicator is equal to or less than the standard range. The manipulator system described in. Using the manipulator according to any one of claims 12 to 18, performing zona pellucida perforation on the egg as the object with the capillary,
Thereafter, the capillary moves to perform at least one sperm sampling operation and then returns to the position of the zona pellucida perforation,
A method for manipulating a micro object, wherein a sperm injection operation is performed while moving the sperm in a capillary by reciprocation of the injector.

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