JP7238434B2 - MANIPULATION SYSTEM AND METHOD FOR DRIVING MANIPULATION SYSTEM - Google Patents

Description

The present invention relates to a manipulation system and a method for driving the manipulation system.

BACKGROUND ART In the field of drug discovery screening, a technique for elucidating the three-dimensional structure of proteins by measuring X-ray diffraction data of crystallized proteins using an X-ray analyzer is known. The crystallized protein is collected one by one from the product liquid, frozen, and placed in an X-ray analyzer.

JP 2017-232065 A

By the way, since crystallized proteins are soft and fragile, they are generally collected manually by skilled workers. However, for drug discovery screening, it is necessary to collect and analyze tens of thousands of crystallized proteins per year, which increases the burden on manual workers.

The present invention has been made in view of the above, and aims to provide a manipulation system and a method for driving the manipulation system that can efficiently and suitably collect crystallized proteins regardless of the skill and skill of the operator. aim.

A manipulation system according to an aspect of the present invention comprises a container for storing a crystallized protein, a sample stage on which the container is placed, a sampling instrument for sampling the crystallized protein, the crystallized protein and the an imaging device that captures an image of a sampling device; positional information of the crystallized protein and the sampling device is detected based on image data of the imaging device; and based on the positional information, the sample stage, the sampling device, and the a controller that controls the imaging device and causes the collection instrument to collect the crystallized protein.

According to this, since the controller detects the positional information of the crystallized protein and the collection device based on the image data, the positional information of the crystallized protein and the collection device can be obtained regardless of the operator's skill and skill level. can be detected. In addition, since the controller automatically controls the detection of the positional information of the crystallized protein and the collection instrument and the control of the movement of the collection instrument, the damage to the crystallized protein is suppressed, and the crystallized protein is efficiently and suitably controlled. Crystallized protein can be collected at

The manipulation system according to one aspect of the present invention further includes an electric motor that rotates the sampling instrument. According to this, the instrument for collection can collect the crystallized protein in a more suitable direction and posture.

In the manipulation system according to one aspect of the present invention, the sampling instrument includes a ring-shaped sampling portion at its tip. According to this, the collecting instrument can hold the product liquid containing the crystallized protein in the area inside the collecting part by the surface tension of the product liquid. Since the crystallized protein does not come into contact with the collecting instrument, damage to the crystallized protein can be suppressed.

In the manipulation system according to one aspect of the present invention, the controller determines whether the crystallized protein has been collected based on the image data of the imaging device. According to this, the controller automatically determines whether or not the crystallized protein has been collected by the collecting device based on the image data, so that the crystals can be efficiently and suitably crystallized regardless of the skill and skill of the operator. It can be determined whether the protein has been collected.

In the manipulation system according to one aspect of the present invention, the controller determines whether the crystallized protein has been collected based on the position information. According to this, the controller automatically determines whether or not the crystallized protein has been collected by the collecting device based on the positional information, so that the crystals can be efficiently and suitably crystallized regardless of the operator's technique and skill. It can be determined whether the protein has been collected.

In the manipulation system according to one aspect of the present invention, the controller determines a predetermined sampling position at which the sampling instrument faces the crystallized protein, based on the positional information. According to this, a suitable collection position can be determined based on the position information detected based on the image data, so that the crystallized protein can be efficiently and suitably collected regardless of the skill and skill of the operator. be able to.

In the manipulation system according to one aspect of the present invention, the controller sets a moving route of the sampling instrument from a predetermined initial position to the predetermined sampling position based on the position information. According to this, a suitable movement route can be determined based on the position information detected based on the image data, so that the crystallized protein can be efficiently and suitably collected regardless of the skill and skill of the operator. be able to.

A manipulation system according to an aspect of the present invention includes a freezing container that contains a freezing liquid and is placed on the sample stage, wherein the controller moves the collecting instrument that has collected the crystallized protein to the freezing container. and freeze the crystallized protein with the freezing liquid. According to this, the control of moving the sampling instrument and the control of freezing the crystallized protein are automatically performed by the controller. can be frozen.

In the manipulation system according to one aspect of the present invention, a collection container placed on the sample stage is provided, and the controller moves the collection instrument that collected the crystallized protein to the collection container, and moves the collection container to the collection container. The instrument is stored in the collection container. According to this, since the controller automatically controls the movement of the collection instrument and the control of storing the crystallized protein in the collection container, the damage to the crystallized protein is suppressed, and the crystallized protein is efficiently and favorably controlled. Crystallized protein can be recovered.

A method of driving a manipulation system according to an aspect of the present invention includes a container containing a crystallized protein, a sample stage on which the container is placed, a collection instrument for collecting the crystallized protein, and the crystallized protein. A method of driving a manipulation system comprising: an imaging device for imaging a protein and the sampling instrument, comprising: causing the imaging device to shoot an image of the crystallized protein and the sampling instrument; and detecting positional information of the crystallized protein and the collecting device based on image data of the collecting device; and collecting the crystallized protein with the collecting device based on the positional information.

According to this method, since the positional information of the crystallized protein and the collection device is detected based on the image data, the positional information of the crystallized protein and the collection device can be detected regardless of the operator's skill and skill level. can be done. In addition, since the control for imaging the crystallized protein and the collection device, the control for detecting the position information of the crystallized protein and the collection device, and the control for moving the collection device are automatically performed, Crystallized protein can be efficiently and suitably collected by suppressing damage.

In the method for driving a manipulation system according to an aspect of the present invention, after collecting the crystallized protein, causing the imaging device to photograph the crystallized protein and the collecting instrument again; determining whether the crystallized protein has been collected based on the image data of the instrument. According to this method, it is automatically determined whether or not the crystallized protein has been collected by the collection device based on the image data, so that the crystallized protein can be efficiently and suitably collected regardless of the operator's technique and skill. It can be determined whether or not it has been collected.

INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide a manipulation system and a method for driving the manipulation system that can efficiently and suitably collect crystallized proteins regardless of the skill and skill of the operator.

FIG. 1 is a perspective view showing a configuration example of a manipulation system according to an embodiment. 2 is an enlarged perspective view of a portion of the manipulation system shown in FIG. 1; FIG. FIG. 3 is a schematic diagram showing a configuration example of the manipulation system according to the embodiment. FIG. 4 is a block diagram showing a configuration example of the manipulation system according to the embodiment. FIG. 5 is a block diagram showing a configuration example of a detection unit. FIG. 6 is a block diagram illustrating a configuration example of a storage unit; FIG. 7 is a diagram illustrating an example of a screen of a display unit; FIG. 8 is a schematic diagram showing a configuration example of a sampling wire probe and a probe holder according to the embodiment. FIG. 9 is a schematic diagram showing an enlarged tip portion of the sampling wire probe according to the embodiment. FIG. 10 is a schematic diagram showing a configuration example of a sampling wire probe and a connection jig according to the embodiment. FIG. 11 is an explanatory diagram for explaining the collection operation of the crystallized protein. FIG. 12 is an explanatory diagram for explaining the operation of the sampling wire probe. FIG. 13 is an explanatory diagram for explaining the operation of the sampling wire probe. FIG. 14 is a diagram showing a sampleable region of the wire probe for sampling. FIG. 15 is a diagram showing a pickable region of the picking wire probe. FIG. 16 is an explanatory diagram explaining the freezing operation of the crystallized protein. FIG. 17 is an explanatory diagram for explaining the recovering operation of the crystallized protein. FIG. 18 is a flow chart diagram showing an example of the operation of the embodiment.

A form (embodiment) for carrying out the present invention will be described in detail with reference to the drawings. The present invention is not limited by the contents described in the following embodiments. In addition, the constituent elements described below include those that can be easily assumed by those skilled in the art, those that are substantially the same, and those that are within a so-called equivalent range. Furthermore, the components described below can be combined as appropriate.

(embodiment)
FIG. 1 is a perspective view showing a configuration example of a manipulation system according to an embodiment. 2 is an enlarged perspective view of a portion of the manipulation system shown in FIG. 1; FIG. FIG. 3 is a schematic diagram showing a configuration example of the manipulation system according to the embodiment. The manipulation system 100 shown in FIGS. 1 to 3 is an apparatus for separating a desired crystallized protein CP (see FIG. 7) from droplets Dr (see FIG. 7) in a container 38 one by one.

As shown in FIGS. 1 to 3, the manipulation system 100 includes a base 1, a sampling wire probe 10, a probe holder 15, a manipulator 20, a sample stage 30, and a first imaging device 45. 1 Microscope unit 40 , controller 50 , second microscope unit 60 including second imaging device 65 , third imaging device 75 , joystick 57 , input unit 58 , and display unit 80 . In the embodiment, the X-axis direction is one direction parallel to the mounting surface 30 a of the sample stage 30 . In the embodiment, the Y-axis direction is parallel to the mounting surface 30a and orthogonal to the X-axis direction. In the embodiment, the Z-axis direction is the normal direction of the mounting surface 30a. The θ-axis direction is a rotation direction about the longitudinal direction of the sampling wire probe 10 as a rotation axis. The placement of the base 1 is adjusted, for example, so that the mounting surface 30a is a horizontal plane perpendicular to the vertical direction.

The collecting wire probe 10 is a collecting instrument for collecting the crystallized protein CP. The details of the sampling wire probe 10 will be described later with reference to FIGS. 8, 9 and 10. FIG.

The probe holding part 15 is an instrument for holding the wire probe 10 for collection. One end of the probe holding portion 15 is connected to the sampling wire probe 10 . The other end of the probe holder 15 is connected to the electric motor 29 of the manipulator 20 . The probe holding portion 15 is connected to the manipulator 20 via a connecting portion 28 which will be described later. Details of the probe holding portion 15 will be described later with reference to FIGS. 8, 9 and 10. FIG.

The manipulator 20 can operate the probe holder 15 and the sampling wire probe 10 by operating in the X-axis direction, the Y-axis direction, and the Z-axis direction. The manipulator 20 includes an X-axis table 21 , a Y-axis table 22 , a Z-axis table 23 , driving devices 26 and 27 , connecting portions 28 and 71 and an electric motor 29 . The X-axis table 21 is moved in the X-axis direction by being driven by the driving device 26 . The Y-axis table 22 is moved in the Y-axis direction by being driven by the driving device 26 . The Z-axis table 23 is moved in the Z-axis direction by being driven by the driving device 27 . Drives 26 , 27 and electric motor 29 are connected to controller 50 .

The connecting portion 28 connects the probe holding portion 15 to the manipulator 20 . The connecting portion 71 connects the lens barrel 411 of the first microscope unit 40 to the manipulator 20 . The connecting portions 28 and 71 are made of metal, for example. The connecting portions 28 and 71 are attached to the Z-axis table 23, for example. Accordingly, the probe holder 15 and the first microscope unit 40 can move in the Z-axis direction by the same distance as the Z-axis table 23 as the Z-axis table 23 moves.

In manipulator 20 , Z-axis table 23 is mounted on Y-axis table 22 . Accordingly, the probe holding section 15 and the first microscope unit 40 can move in the Y-axis direction by the same distance as the Y-axis table 22 as the Y-axis table 22 moves. Furthermore, the Y-axis table 22 is mounted on the X-axis table 21 . Accordingly, the probe holder 15 and the first microscope unit 40 can move in the X-axis direction by the same distance as the X-axis table 21 as the X-axis table 21 moves. In this manner, the probe holding section 15 and the first microscope unit 40 are fixed to each other via the connecting sections 28 and 71 . The probe holding section 15 and the first microscope unit 40 can move integrally in the X-axis direction, the Y-axis direction, and the Z-axis direction according to the operation of the manipulator 20 .

A sample stage 30 supports a container 38 . For example, the container 38 is mounted on the mounting surface 30 a of the sample stage 30 . Container 38 is a well plate in an embodiment. Container 38 includes, in embodiments, six wells 38a. A well 38a of the container 38 accommodates a droplet Dr containing the crystallized protein CP (see FIG. 7). The sample stage 30 includes an X-axis stage 31 , a Y-axis stage 32 and a drive device 36 . The X-axis stage 31 is moved in the X-axis direction by being driven by the driving device 36 . The Y-axis stage 32 is moved in the Y-axis direction by being driven by the driving device 36 . The X-axis stage 31 is mounted on the Y-axis stage 32 . Drive 36 is connected to controller 50 .

In the embodiment, one container 38 is placed on the sample stage 30, but the number of containers 38 placed on the sample stage 30 is not limited to one, and is plural. It's okay. Although the container 38 has a rectangular planar shape in the embodiment, it may have a non-rectangular shape, for example, a circular shape. Container 38 may be a petri dish or dish. In the embodiment, the sample stage 30 has a rectangular shape in plan view (hereinafter referred to as a planar shape), but the shape may not be rectangular, and may be circular, for example.

The first microscope unit 40 is arranged above the sample stage 30 . The first microscope unit 40 includes a first microscope 41 , a first imaging device 45 , and a light source that emits light toward the mounting surface 30 a of the sample stage 30 . The first microscope 41 includes a lens barrel 411 , an objective lens 412 and a driving device 414 . The first microscope 41 is a stereomicroscope with an objective lens 412 located above the container 38 . The objective lens 412 is moved in the Z-axis direction by being driven by the driving device 414 . Thereby, the first microscope 41 can adjust the focal position. A plurality of types of the objective lens 412 may be prepared according to the desired magnification. The first imaging device 45 includes, for example, a solid-state imaging device such as a CMOS image sensor or a CCD image sensor. The first imaging device 45 can image the tip of the sampling wire probe 10 from the Z-axis direction via the first microscope 41 . The first microscope unit 40 may comprise an eyepiece. The first microscope unit 40 is driven by the drive device 414 to move in the Z-axis direction. The driving device 414 is driven by a control section 55 which will be described later. The lens barrel 411 is connected to the manipulator 20 by a connecting portion 71 . As a result, the manipulator 20, the probe holder 15, and the wire probe 10 for sampling move in the Z-axis direction in accordance with the motion of the first microscope unit 40 in the Z-axis direction.

The second microscope unit 60 is arranged on the side of the sample stage 30 . The second microscope unit 60 includes a second microscope 61 and a second imaging device 65 . The second microscope 61 includes a lens barrel 611 , an objective lens 612 and a driving device 613 . The objective lens 612 is moved in the Y-axis direction by being driven by the driving device 613 . Thereby, the second microscope 61 can adjust the focal position. The second imaging device 65 includes, for example, a solid-state imaging device such as a CMOS image sensor or a CCD image sensor. The second imaging device 65 can image the tip of the sampling wire probe 10 from the Y-axis direction via the second microscope 61 . The second microscope unit 60 is fixed to the base 1 via the fixture 3 .

The third imaging device 75 is fixed to the base 1 via the fixture 4 . The fixture 4 can move in the X-axis direction and the Y-axis direction, and can extend in the Z-axis direction. Thereby, the third imaging device 75 can image the sample stage 30 side from an obliquely upward direction of the sample stage 30 that intersects with the X-axis direction, the Y-axis direction, and the Z-axis direction.

The input unit 58 is a keyboard, touch panel, or the like. The joystick 57 and input section 58 are connected to the controller 50 . An operator can input commands to the controller 50 via the joystick 57 and the input unit 58 . A control signal Vsig1 is output from the joystick 57 to the controller 50 by the operator operating the joystick 57 . A control signal Vsig<b>2 is output from the input unit 58 to the controller 50 when the operator operates the input unit 58 .

Next, functions of the controller 50 will be described with reference to FIG. FIG. 4 is a block diagram showing a configuration example of the manipulation system according to the embodiment. The controller 50 includes hardware resources such as a CPU (Central Processing Unit) as computing means, a hard disk as storage means, a RAM (Random Access Memory), and a ROM (Read Only Memory).

As shown in FIG. 4, the controller 50 has functions such as an image input unit 51a, an image output unit 51b, an image processing unit 52, a detection unit 53, an image editing unit 54, a control unit 55, and a storage unit. a portion 56; The image input unit 51a, the image output unit 51b, the image processing unit 52, the detection unit 53, the image editing unit 54, and the control unit 55 are implemented by the above computing means. The storage unit 56 is implemented by the storage means described above. The controller 50 performs various calculations based on the programs stored in the storage unit 56, and outputs drive signals so that the control unit 55 performs various controls according to the calculation results.

The control unit 55 controls the driving device 414 of the first microscope unit 40, the driving devices 26 and 27 and the electric motor 29 of the manipulator 20, the driving device 36 of the sample stage 30, and the driving device 613 of the second microscope unit 60. Control. The controller 55 supplies drive signals Vz1, Vxy2, Vz2, Vxy3 and Vy4 (see FIG. 3) to the drive devices 414, 26, 27, 36 and 613, respectively. The controller 55 supplies the electric motor 29 with a drive signal Vθ (see FIG. 3). The control unit 55 may supply the drive signals Vz1, Vxy2, Vz2, Vxy3, Vy4, and Vθ through drivers, amplifiers, etc. provided as necessary.

The first image signal Vpix1 (see FIG. 3) output from the first imaging device 45, the second image signal Vpix2 (see FIG. 3) output from the second imaging device 65, and the output from the third imaging device 75 The third image signal Vpix3 (see FIG. 3) is input to the image input unit 51a. The image processing unit 52 receives the first image signal Vpix1, the second image signal Vpix2, and the third image signal Vpix3 from the image input unit 51a and performs image processing. The image output unit 51 b outputs the image information image-processed by the image processing unit 52 to the storage unit 56 and the display unit 80 .

For example, the first image signal Vpix1 includes the first image captured by the first imaging device 45 through the first microscope 41 and the imaging time. The first image is a moving image. Similarly, the second image signal Vpix2 includes the second image captured by the second imaging device 65 through the second microscope 61 and its imaging time. The second image is also a moving image. The third image signal Vpix3 includes the third image captured by the third imaging device 75 and its imaging time. The third image is also a moving image.

The first image, the second image and the third image are color images or gray images, respectively. A gray image is an image containing white, black, and gray that is an intermediate color between white and black. A gray image includes multiple shades of gray. Gradation is the number of steps of color and brightness.

The image processing unit 52 performs image processing such as image enlargement and binarization on at least one of the first image and the second image in order to facilitate detection of the crystallized protein CP (see FIG. 7). Binarization of an image means converting a color image or a gray image (hereinafter referred to as an original image) into a binary image having only white and black without shading. The image processing unit 52 generates an enlarged image obtained by enlarging the original image or a binary image obtained by binarizing the original image for at least one of the first image and the second image. The image processing unit 52 may enlarge the original image and generate an enlarged binary image that is binarized. The image processing unit 52 outputs at least one of an enlarged image, a binary image, and an enlarged binary image to the detection unit 53 and the image editing unit 54 as image information.

The detection unit 53 receives the image information from the image processing unit 52, and automatically detects the position and the number of the crystallized protein CP (see FIG. 7) based on the received image information. Then, the detection section 53 outputs the detection result to the image editing section 54 and the storage section 56 .

FIG. 5 is a block diagram showing a configuration example of a detection unit. As shown in FIG. 5, the detection unit 53 includes a position detection unit 531, a distance detection unit 532, and a number detection unit 533 as its functions. The position detection unit 531 automatically detects the position of the crystallized protein CP (see FIG. 7) based on the first image or the second image image-processed by the image processing unit 52 . The distance detection unit 532 automatically detects the separation distance between the crystallized protein CP detected by the position detection unit 531 and the loop portion 101 of the collection wire probe 10 (see FIG. 9 described later). The number detection unit 533 automatically detects the position and number of the crystallized protein CP based on the first image or the second image image-processed by the image processing unit 52 . Examples of images that have undergone image processing by the image processing unit 52 include at least one or more of an enlarged image, a binary image, and an enlarged binary image. The detection results of the position detection unit 531, the distance detection unit 532, and the number detection unit 533 are output to the image editing unit 54 and the storage unit 56, respectively.

The image editing unit 54 associates the first image signal Vpix1, the second image signal Vpix2, and the third image signal Vpix3 with each other based on the imaging time to generate the edited image signal Vpix4. The edited image signal Vpix4 contains an edited image. An edited image is a moving image in which a first image, a second image, and a third image captured at the same time are displayed side by side. In the edited image, the first image, the second image, and the third image may each be the original image, or an enlarged image obtained by image processing the original image, a binary image, or an enlarged binary image. The image output unit 51b outputs the first image signal Vpix1, the second image signal Vpix2, the third image signal Vpix3, and the edited image signal Vpix4 to the storage unit 56. FIG.

The image editor 54 receives the detection result of the crystallized protein CP (see FIG. 7) from the detector 53 . When the detection unit 53 detects the position of the crystallized protein CP, the image editing unit 54 may reflect the detection result in the edited image. For example, the image editing unit 54 automatically indicates with an arrow the position of the crystallized protein CP detected by the detection unit 53 in the enlarged image, the binary image, or the enlarged binary image received from the image processing unit 52. The position of the crystallized protein CP detected by 53 may be automatically surrounded by a border.

FIG. 6 is a block diagram illustrating a configuration example of a storage unit; As shown in FIG. 6, the storage unit 56 includes, as its functions, a program storage unit 56a storing a program for operating the manipulation system 100, and an image storage unit 56b storing image signals. The image storage unit 56b includes a first image storage unit 561 that stores the first image signal Vpix1, a second image storage unit 562 that stores the second image signal Vpix2, and a third image storage unit that stores the third image signal Vpix3. and an edited image storage unit 564 that stores the edited image signal Vpix4.

The image output unit 51b outputs at least one or more of the first image signal Vpix1, the second image signal Vpix2, the third image signal Vpix3, and the edited image signal Vpix4 to the display unit 80 (see FIG. 3). . The image output unit 51 b selects an image signal to be output to the display unit 80 according to the control signal Vsig<b>1 input to the controller 50 and outputs the selected image signal to the display unit 80 . The image output unit 51 b may select an image signal to be output to the display unit 80 according to the control signal Vsig<b>2 input to the controller 50 and output the selected image signal to the display unit 80 .

The display unit 80 is, for example, a liquid crystal panel or the like. The display unit 80 is connected to the controller 50 . The display unit 80 displays various character information, images, etc. on the screen. FIG. 7 is a diagram illustrating an example of a screen of a display unit; FIG. 7 illustrates a case where an edited image is displayed on the screen 81 of the display section 80. As shown in FIG. In the edited image, a first image 811, a second image 812, and a third image 813 captured at the same timing are arranged side by side. The display unit 80 may display the edited image in real time or substantially in real time, or may read out and display the edited image stored in the edited image storage unit 564 .

The image displayed on the screen 81 can be switched by the operator operating the joystick 57 or the input unit 58 . By operating the joystick 57 or the input unit 58 by the operator, it is possible to pause the edited image (moving image) displayed on the screen 81 . Based on the program stored in the program storage unit 56a (see FIG. 6), the control unit 55 (see FIG. 4) automatically displays a predetermined image on the screen 81 or automatically changes the image displayed on the screen 81. You can switch with .

The image displayed on the screen 81 is not limited to the edited image, and may be the first image 811, the second image 812, or the third image 813 alone. The image displayed on the screen 81 is not limited to the original image, and may be an image that has undergone image processing by the image processing unit 52 (for example, at least one of an enlarged image, a binary image, and an enlarged binary image). There may be. For example, the images displayed on the screen 81 may be a first image 811, an enlarged image obtained by enlarging a part of the first image 811, and an enlarged binary image obtained by binarizing the enlarged image. good.

FIG. 8 is a schematic diagram showing a configuration example of a sampling wire probe and a probe holder according to the embodiment. FIG. 9 is a schematic diagram showing an enlarged tip portion of the sampling wire probe according to the embodiment. FIG. 10 is a schematic diagram showing a configuration example of a sampling wire probe and a connection jig according to the embodiment.

The collecting wire probe 10 is a collecting instrument for collecting the crystallized protein CP. The sampling wire probe 10 is a needle-like instrument. One end of the collecting wire probe 10 includes a loop portion 101 for collecting the crystallized protein CP. The other end of the sampling wire probe 10 includes a connecting portion 102 .

The loop part 101 is a collecting part for collecting the crystallized protein CP. The loop portion 101 has a ring shape including a central axis in a direction crossing the longitudinal direction of the sampling wire probe 10 . Loop portion 101 collects crystallized protein CP in a region surrounded by inner peripheral surface 101a. The loop portion 101 holds the droplet Dr containing the crystallized protein CP in the region surrounded by the inner peripheral surface 101a by the surface tension of the droplet Dr.

Connection 102 includes a magnet in this embodiment. The connecting portion 102 is connected to one end of the probe holding portion 15 . The connecting portion 102 is detachably connected to a connecting portion 154 of the probe holding portion 15 described later by magnetic force (see FIG. 17 described later).

The probe holding part 15 is an instrument for holding the wire probe 10 for collection. The probe holding section 15 includes a main body 151 , a centering mechanism 152 , a connection jig 153 and a connection section 154 .

The main body 151 is connected to the manipulator 20 via the connecting portion 28 shown in FIG. The main body 151 is moved in the X-axis direction, the Y-axis direction, and the Z-axis direction by the manipulator 20 driven based on the drive signal from the controller 50 . The main body 151 has the electric motor 29 mounted thereon.

The centering mechanism 152 is a mechanism that rotates the sampling wire probe 10 in the θ-axis direction via the connection jig 153 . The centering mechanism 152 is provided on the main body 151 . The centering mechanism 152 rotates the connection jig 153 in the θ-axis direction. The centering mechanism 152 rotates the connection jig 153 in the θ-axis direction by the electric motor 29 driven based on the drive signal from the controller 50 .

The connection jig 153 is a rod-shaped instrument. One end of the connection jig 153 is connected to the end of the sampling wire probe 10 opposite to the loop portion 101 . One end of the connecting jig 153 includes a connecting portion 154 . The other end of the connection jig 153 is connected to the centering mechanism 152 . The connection jig 153 is supported by the centering mechanism 152 . The connection jig 153 is connected to the main body 151 via the centering mechanism 152 .

Connection 154 includes a magnet in this embodiment. The connecting portion 154 is connected to the end of the sampling wire probe 10 opposite to the loop portion 101 . The connecting portion 154 is detachably connected to the connecting portion 102 of the wire probe 10 for sampling by magnetic force (see FIG. 17).

Next, the collection operation of the crystallized protein CP by the collection wire probe 10 will be described. As shown in FIG. 7, crystallized protein CP is produced in well 38a of container 38. As shown in FIG. Manipulation system 100 picks up droplet Dr containing crystallized protein CP in well 38a. FIG. 11 is an explanatory diagram for explaining the collection operation of the crystallized protein. 12 and 13 are explanatory diagrams for explaining the operation of the sampling wire probe. 14 and 15 are diagrams showing the pickable region of the wire probe for picking.

As shown in FIG. 11 , the manipulation system 100 collects the crystallized protein CP using the loop portion 101 of the collection wire probe 10 . The manipulation system 100 first inserts the loop portion 101 into the droplet Dr containing the crystallized protein CP. The manipulation system 100 then causes the loop portion 101 to slip under the crystallized protein CP. At this time, when viewed in the Z-axis direction, the opening of the loop portion 101 is positioned to enter the crystallized protein CP. The manipulation system 100 then moves the loop portion 101 so that the crystallized protein CP passes through the region surrounded by the inner peripheral surface 101a (see FIG. 9) of the loop portion 101. FIG. Thereby, the loop portion 101 holds the droplet Dr containing the crystallized protein CP in the region surrounded by the inner peripheral surface 101a by the surface tension of the droplet Dr. The loop part 101 picks up the crystallized protein CP together with the droplet Dr.

The loop portion 101 can be driven in at least one of the X-axis direction, Y-axis direction, Z-axis direction, and θ-axis direction by the manipulator 20 and the centering mechanism 152 . Thereby, the loop part 101 can collect the crystallized protein CP from various directions.

For example, as shown in FIG. 12, loop portion 101 may collect crystallized protein CP from below. It is assumed that the loop portion 101 is arranged at a position separated from the crystallized protein CP in the X-axis direction. The controller 50 first moves the loop portion 101 in the X-axis direction to get under the crystallized protein CP. The controller 50 then moves the loop portion 101 in the Z-axis direction to pick up the crystallized protein CP from below. In this manner, the loop portion 101 can be controlled by the manipulator 20 in the X-axis direction and the Z-axis direction so as to pick up the crystallized protein CP from below.

For example, as shown in FIG. 13, the loop portion 101 may collect the crystallized protein CP from the side. It is assumed that the loop portion 101 is arranged at a position separated from the crystallized protein CP in the X-axis direction and the Y-axis direction. The controller 50 first rotates the loop portion 101 in the θ-axis direction to tilt the normal direction of the opening of the loop portion 101 with respect to the XZ plane. The controller 50 then moves the loop portion 101 in the X-axis direction. At this time, the crystallized protein CP is positioned inside the inner circumferential surface 101a of the loop portion 101 as viewed in the Y-axis direction. Next, the controller 50 moves the loop portion 101 in the Y-axis direction and picks up the crystallized protein CP from the side. In this way, the loop portion 101 can pick up the crystallized protein CP from the side by controlling the manipulator 20 in the θ-axis direction, the X-axis direction, and the Y-axis direction.

When the loop part 101 collects the crystallized protein CP from below, the loop part 101 needs to be arranged so that the crystallized protein CP is located inside the inner peripheral surface 101a of the loop part 101 when viewed in the Z-axis direction. (see FIG. 12). As shown in FIG. 14, when the loop portion 101 is moved in the Z-axis direction to collect the crystallized protein CP, the harvestable region CZ1 is inside the inner peripheral surface 101a of the loop portion 101 when viewed from the Z-axis direction. is an elliptical region in . As described above, when the crystallized protein CP is collected by moving the loop portion 101 in any of the X-axis direction, the Y-axis direction, and the Z-axis direction, the harvestable region CZ1 is , an elliptical area inside the inner peripheral surface 101 a of the loop portion 101 . The loop portion 101 is arranged so that the crystallized protein CP is positioned within the harvestable region CZ1 immediately before the crystallized protein CP is harvested.

As shown in FIG. 15, when the loop portion 101 is rotated in the θ-axis direction to collect the crystallized protein CP, the harvestable region CZ2 becomes the inner circumference when the loop portion 101 is rotated once in the θ-axis direction. It is a spherical area formed by the trajectory of the surface 101a. The loop portion 101 is arranged so that the crystallized protein CP is positioned within the harvestable region CZ2 immediately before the crystallized protein CP is harvested.

The collection position of the crystallized protein CP and the movement path of the loop part 101 are set based on the previously detected position, orientation and shape of the loop part 101 and the position of the crystallized protein CP. The collection position of the crystallized protein CP is the position of the loop portion 101 when the crystallized protein CP exists in the region surrounded by the inner peripheral surface 101a of the loop portion 101 . The movement route of the loop portion 101 is the route along which the loop portion 101 moves from the initial position to the collection position. The movement path is a combination of movements in the X-axis direction, Y-axis direction, Z-axis direction, and θ-axis direction.

The image processing section 52 of the controller 50 shown in FIG. 4 performs image processing on the image data of the loop section 101 and the crystallized protein CP captured by the first, second, and third imaging devices 45, 65, and 75, respectively. The detector 53 of the controller 50 detects the position, orientation and shape of the loop part 101 and the position of the crystallized protein CP by image processing. After the loop unit 101 performs the collection operation, the image processing unit 52 acquires the image data of the loop unit 101 . The detector 53 detects the position of the crystallized protein CP from the image data. The control unit 55 of the controller 50 determines whether or not the crystallized protein CP has been successfully collected based on the obtained positional information of the crystallized protein CP.

FIG. 16 is an explanatory diagram explaining the freezing operation of the crystallized protein. Manipulation system 100 moves crystallized protein CP harvested from container 38 to freezing container 37 . A cryocontainer 37 may, for example, be placed on the sample stage 30 adjacent to the container 38 . The cryocontainer 37 may be placed anywhere within a reach of the sampling wire probe 10 by driving the manipulator 20 and the sample stage 30 .

The inside of the freezing container 37 is filled with a freezing liquid. The freezing liquid is liquid nitrogen LN in this embodiment. The manipulation system 100 submerges the loop portion 101 holding the crystallized protein CP in liquid nitrogen LN to freeze the crystallized protein CP.

FIG. 17 is an explanatory diagram for explaining the recovering operation of the crystallized protein. The manipulation system 100 moves the crystallized protein CP frozen in the freezing container 37 to the collection container 39 . The collection container 39 may be arranged on the sample stage 30 adjacent to at least one of the container 38 and the freezing container 37, for example. The collection container 39 may be placed anywhere within a reach of the collection wire probe 10 by driving the manipulator 20 and the sample stage 30 .

The collection container 39 includes a storage portion 39 a that stores the loop portion 101 . The storage portion 39a is cylindrical in this embodiment. The collection container 39 is installed such that the longitudinal direction of the storage portion 39 a coincides with the longitudinal direction of the sampling wire probe 10 . The opening of the storage portion 39a has a structure that can be closed by the end of the sampling wire probe 10 opposite to the loop portion 101 . The opening of the storage portion 39a is closed by the connecting portion 102 of the sampling wire probe 10 in this embodiment. In the collecting container 39, the collection wire probe 10 is stored in the storage portion 39a, and the connection portion 102 of the collection wire probe 10 and the connection portion 154 of the probe holding portion 15 are disconnected to release the collection wire. Only the probe 10 is recovered. In the present embodiment, since the connection portion 102 and the connection portion 154 include magnets, the connection portion 102 and the connection portion 154 can be easily connected by moving the connection jig 153 in a direction intersecting the longitudinal direction. can be released.

Next, a method for collecting and recovering the crystallized protein CP in the manipulation system 100 will be described. Before starting the operation of the manipulation system 100, the operator first attaches the sampling wire probe 10 shown in FIG. The operator then places the sampling wire probe 10 within the fields of view of the first microscope 41 , the second microscope 61 and the third imaging device 75 . Here, the height of the tip of the sampling wire probe 10 is at least higher than the height at which the container 38 is installed. The operator then places the container 38 containing the droplet Dr containing the crystallized protein CP to be sampled on the sample stage 30 . The operator then moves the sample stage 30 so that the well 38 a of the container 38 overlaps the fields of view of the first microscope 41 , the second microscope 61 and the third imaging device 75 . The operator then moves the objective lens 412 of the first microscope 41 by driving the driving device 414 to focus the first microscope 41 on the crystallized protein CP. The operator moves the objective lens 612 of the second microscope 61 by driving the driving device 613 to focus the second microscope 61 on the crystallized protein CP.

FIG. 18 is a flow chart diagram showing an example of the operation of the embodiment. The manipulation system 100 performs manipulations on one crystallized protein CP. The controller 50 automatically executes operations on the crystallized protein CP. Automatic operation by the manipulation system 100 is started by pressing a start button of the input unit 58, for example.

First, in step ST10, the image processing section 52 of the controller 50 acquires the image data of the loop section 101 captured by the first imaging device 45, the second imaging device 65, and the third imaging device 75. FIG. The image processing unit 52 performs image processing on image data. In step ST12, the detection unit 53 of the controller 50 detects the position, orientation and shape of the loop unit 101 by image processing. The storage unit 56 stores information on the position, orientation and shape of the loop unit 101 .

Next, in step ST14, the image processing unit 52 acquires image data of the crystallized protein CP captured by the first imaging device 45, the second imaging device 65, and the third imaging device 75. FIG. The image processing unit 52 performs image processing on image data. In step ST16, the detection unit 53 detects the position of the crystallized protein CP by image processing. The storage unit 56 stores the position information of the crystallized protein CP.

In step ST18, the control unit 55 sets the collection position of the crystallized protein CP and the movement path of the collection wire probe 10 based on the information of the loop unit 101 and the crystallized protein CP stored in the storage unit 56. The control unit 55 causes the storage unit 56 to store the movement distance and order in the X-axis direction, Y-axis direction, Z-axis direction, and θ-axis direction. In step ST20, the control unit 55 drives the manipulator 20 to move the collection wire probe 10 to the collection position of the crystallized protein CP along the movement path. In step ST22, the control section 55 drives the manipulator 20 to allow the wire probe 10 for collection to collect the crystallized protein CP. Step ST20 and step ST22 may be executed continuously or may be executed as a series of operations.

In step ST<b>24 , the image processing unit 52 acquires image data of the loop unit 101 captured by the first imaging device 45 , the second imaging device 65 and the third imaging device 75 . The image processing unit 52 performs image processing on image data. In step ST26, the detection unit 53 detects the position of the crystallized protein CP by image processing.

In step ST28, the control unit 55 determines whether or not the crystallized protein CP has been successfully collected based on the positional information of the crystallized protein CP. For example, when the crystallized protein CP is not located in the region surrounded by the inner peripheral surface 101a of the loop portion 101, the control unit 55 determines that the collection of the crystallized protein CP has failed. In step ST28, if the collection of the crystallized protein CP fails (step ST28; No), the process proceeds to step ST14. For example, when the crystallized protein CP is located in the region surrounded by the inner peripheral surface 101a of the loop portion 101, the controller 55 determines that the crystallized protein CP has been successfully collected. In step ST28, when the collection of the crystallized protein CP is successful (step ST28; Yes), the process proceeds to step ST30.

In step ST<b>30 , the controller 55 drives the manipulator 20 and the sample stage 30 to move the sampling wire probe 10 to the cryocontainer 37 . In step ST32, the control unit 55 drives the manipulator 20 to submerge the sampling wire probe 10 in the liquid nitrogen LN filled in the freezing container 37, thereby freezing the crystallized protein CP held in the loop unit 101. For example, when a preset time has elapsed, the control unit 55 pulls up the sampling wire probe 10 from the freezing container 37 .

In step ST<b>34 , the control unit 55 drives the manipulator 20 and the sample stage 30 to move the wire probe 10 for collection to the collection container 39 . At this time, the control unit 55 moves the sampling wire probe 10 so that the longitudinal direction of the sampling wire probe 10 and the longitudinal direction of the storage portion 39a of the collection container 39 are aligned. In step ST<b>36 , the control section 55 drives the manipulator 20 to insert the sampling wire probe 10 into the storage section 39 a of the collection container 39 . The control unit 55 drives the manipulator 20 to separate the probe holding unit 15 from the sampling wire probe 10 . The control unit 55 releases the connection between the connecting portion 102 of the sampling wire probe 10 and the connecting portion 154 of the probe holding portion 15 . As a result, only the sampling wire probe 10 is stored in the storage portion 39 a of the collection container 39 . The housing portion 39a is closed by the connecting portion 102 of the wire probe 10 for sampling.

In step ST38, the control section 55 drives the manipulator 20 to move the probe holding section 15 to the initial position. When the probe holder 15 returns to the initial position, the manipulation system 100 completes a series of operations.

As described above, the manipulation system 100 of the present embodiment includes the container 38, the sample stage 30, the sampling instrument (sampling wire probe 10), the imaging devices (first imaging device 45, second imaging device 65). and a third imaging device 75 ) and a controller 50 . A container 38 accommodates the crystallized protein CP. A container 38 is placed on the sample stage 30 . A collection instrument collects the crystallized protein CP. The imaging device images the crystallized protein CP and the collection device. The controller 50 detects the positional information of the crystallized protein CP and the sampling instrument based on the image data of the imaging device. The controller 50 controls the sample stage 30, the collecting device, and the imaging device based on the positional information, and causes the collecting device to collect the crystallized protein CP.

According to this, since the controller 50 detects the position information of the crystallized protein CP and the sampling instrument (sampling wire probe 10) based on the image data, crystallization can be performed regardless of the operator's skill and skill. It is possible to detect the location information of the protein CP and the collection device. In addition, since the controller 50 automatically controls the detection of the positional information of the crystallized protein CP and the collection tool and the control of the movement of the collection tool, damage to the crystallized protein CP is suppressed and efficiency is improved. A good and suitable crystallized protein CP can be harvested.

The manipulation system 100 of this embodiment further includes an electric motor 29 that rotates the sampling instrument. According to this, the instrument for collection can collect the crystallized protein CP in a more suitable direction and posture.

In the manipulation system 100 of this embodiment, the sampling instrument (sampling wire probe 10) includes a ring-shaped sampling portion (loop portion 101) at its tip. According to this, the collecting instrument spreads the generated liquid (droplet Dr) containing the crystallized protein CP in the region inside the collecting portion (the region surrounded by the inner peripheral surface 101a) by the surface tension of the generated liquid. can hold. Since the crystallized protein CP does not come into contact with the collecting instrument, damage to the crystallized protein CP can be suppressed.

In the manipulation system 100 of the present embodiment, the controller 50 determines whether the crystallized protein CP has been collected based on the image data of the imaging devices (the first imaging device 45, the second imaging device 65, and the third imaging device 75). to judge whether According to this, the controller 50 automatically determines whether or not the crystallized protein CP has been collected by the collecting device (collecting wire probe 10) based on the image data. Whether or not the crystallized protein CP has been collected can be efficiently and suitably determined regardless of whether the crystallized protein CP has been collected.

In the manipulation system 100 of this embodiment, the controller 50 determines whether or not the crystallized protein CP has been collected based on the positional information. According to this, the controller 50 automatically determines whether or not the crystallized protein CP has been collected by the collecting device (collecting wire probe 10) based on the positional information. Whether or not the crystallized protein CP has been collected can be efficiently and suitably determined regardless of whether the crystallized protein CP has been collected.

In the manipulation system 100 of this embodiment, the controller 50 determines a predetermined sampling position where the sampling instrument (sampling wire probe 10) faces the crystallized protein CP based on the position information. According to this, since a suitable collection position can be determined based on the position information detected based on the image data, the crystallized protein CP can be efficiently and suitably collected regardless of the skill and skill of the operator. can do.

In the manipulation system 100 of the present embodiment, the controller 50 sets the movement route of the sampling instrument (sampling wire probe 10) from a predetermined initial position to a predetermined sampling position based on position information. According to this, a suitable movement route can be determined based on the position information detected based on the image data, so that the crystallized protein CP can be efficiently and suitably collected regardless of the skill and skill of the operator. can do.

The manipulation system 100 of this embodiment includes a cryocontainer 37 that contains a cryofluid (liquid nitrogen LN) and is mounted on the sample stage 30 . In the manipulation system 100 of this embodiment, the controller 50 moves the sampling instrument (sampling wire probe 10) that has sampled the crystallized protein CP to the freezing container 37, and freezes the crystallized protein CP with the freezing liquid. According to this, the control of moving the collection instrument and the control of freezing the crystallized protein CP are automatically performed by the controller 50, so damage to the crystallized protein CP is suppressed, and the crystallized protein CP is efficiently and preferably Crystallized protein CP can be frozen.

The manipulation system 100 of this embodiment includes a collection container 39 placed on the sample stage 30 . In the manipulation system 100 of the present embodiment, the controller 50 moves the collecting instrument (collecting wire probe 10 ) that collected the crystallized protein CP to the collection container 39 and stores the collecting instrument in the collection container 39 . According to this, the controller 50 automatically controls the movement of the sampling instrument and the control of storing the crystallized protein CP in the collection container 39, thereby suppressing damage to the crystallized protein CP and improving efficiency. The crystallized protein CP can be recovered well and favorably.

A driving method of the manipulation system 100 of the present embodiment is as follows. , a second imaging device 65 and a third imaging device 75 ) and a controller 50 . A container 38 accommodates the crystallized protein CP. A container 38 is placed on the sample stage 30 . A collection instrument collects the crystallized protein CP. The imaging device images the crystallized protein CP and the collection device. The driving method of the manipulation system 100 consists of the step of causing the imaging device to photograph the crystallized protein CP and the sampling tool (steps ST10 and ST14), and the step of capturing the crystallized protein CP based on the image data of the crystallized protein CP and the sampling tool. and detecting the positional information of the collecting device (steps ST12 and ST16), and the step of collecting the crystallized protein CP with the collecting device based on the positional information (steps ST18, steps ST20 and ST22). .

According to this, since the position information of the crystallized protein CP and the sampling instrument (sampling wire probe 10) is detected based on the image data, the crystallized protein CP and the sampling device can be detected regardless of the skill and skill of the operator. It is possible to detect the position information of the equipment. In addition, since the control for imaging the crystallized protein CP and the collection instrument, the control for detecting the position information of the crystallized protein CP and the collection instrument, and the control for moving the collection instrument are automatically performed, the crystallization Crystallized protein CP can be collected efficiently and suitably by suppressing damage to protein CP.

In the driving method of the manipulation system 100 of the present embodiment, after the crystallized protein CP is collected, the crystallized protein CP and the collected crystallized protein CP are again captured by the imaging devices (the first imaging device 45, the second imaging device 65, and the third imaging device 75). (step ST24 and step ST26), and determining whether or not the crystallized protein CP has been collected based on the image data of the crystallized protein CP and the collection device. and ST28. According to this method, it is automatically determined whether or not the crystallized protein CP has been collected by the collecting device based on the image data, so that the crystallized protein can be obtained efficiently and preferably regardless of the operator's technique and skill. It can be determined whether the CP has been harvested.

The manipulation system 100 of this embodiment and the driving method of the manipulation system 100 may be changed as appropriate. For example, the loop portion 101 of the sampling wire probe 10 has a ring shape in the present embodiment, but may have a C shape. The shape of the loop portion 101 is not limited as long as the droplet Dr containing the crystallized protein CP can be held by the surface tension of the droplet Dr. Moreover, the sampling instrument for sampling the crystallized protein CP is not limited to the sampling wire probe 10 . The manipulation system may include a hollow capillary tube and a micropump instead of the sampling wire probe 10 . In this case, the manipulation system harvests the crystallized protein CP by adjusting the pressure inside the capillary with a micropump and entraining the crystallized protein CP inside the capillary. A part of the procedure for collecting the crystallized protein CP may be appropriately omitted or the procedure may be replaced without departing from the gist of the present invention. Further, in the present embodiment, the operator manually attaches the sampling wire probe 10 to the probe holding portion 15, but it may be attached automatically by the manipulation system 100 or another device.

Reference Signs List 1 base 3, 4 fixture 10 sampling wire probe 101 loop portion 101a inner peripheral surface 102 connection portion 15 probe holding portion 151 main body 152 centering mechanism 153 connection jig 154 connection portion 20 manipulator 21 X-axis table 22 Y-axis table 23 Z-axis table 26, 27 drive device 28, 71 connecting part 29 electric motor 30 sample stage 30a mounting surface 31 X-axis stage 32 Y-axis stage 36 drive device 37 freezing container 38 container 38a well 39 recovery container 39a storage unit 40 first Microscope unit 41 First microscope 411 Lens barrel 412 Objective lens 414 Driving device 45 First imaging device 50 Controller 51a Image input section 51b Image output section 52 Image processing section 53 Detection section 531 Position detection section 532 Distance detection section 533 Number detection section 54 Image editing section 55 Control section 56 Storage section 56a Program storage section 56b Image storage section 561 First image storage section 562 Second image storage section 563 Third image storage section 564 Edited image storage section 57 Joystick 58 Input section 60 Second microscope unit 61 second microscope 611 barrel 612 objective lens 613 driving device 65 second imaging device 75 third imaging device 80 display unit 81 screen 811 first image 812 second image 813 third image 100 manipulation system CP crystallized protein Dr droplet LN Liquid nitrogen CZ1, CZ2 Collectable area

Claims (11)

a container containing a droplet containing the crystallized protein;
a sample stage on which the container is placed;
a collecting instrument that includes a ring-shaped collecting portion at its tip and collects the crystallized protein in a region surrounded by the inner peripheral surface of the collecting portion ;
an electric motor for rotating the sampling instrument around a rotation axis orthogonal to the central axis of the sampling part;
an imaging device that images the crystallized protein and the collection instrument;
a controller that detects the positional information of the crystallized protein and the sampling device based on the image data of the imaging device, and controls the sample stage, the sampling device, and the imaging device based on the positional information;
with
The controller is
The crystallized protein is located inside the harvestable region, which is the region formed by the trajectory of the inner peripheral surface of the sampling portion when the sampling instrument is linearly moved or rotated around the rotation axis. and moving the collecting device linearly or rotating it around the rotation axis so that the crystallized protein passes through the region surrounded by the inner peripheral surface of the collecting portion. a manipulation system that causes the harvesting unit to harvest the crystallized protein . The extractable area is an area that can be seen inside the inner peripheral surface of the extracting portion when viewed from one direction,
the controller causes the collecting unit to collect the crystallized protein by moving the collecting instrument in one direction;
The manipulation system of claim 1. The collectable region is a spherical region formed by the trajectory of the inner peripheral surface of the collecting portion when the collecting portion is rotated around the rotation axis once,
The controller causes the collecting unit to collect the crystallized protein by rotating the collecting instrument around the rotation axis.
The manipulation system of claim 1. 4. The manipulation system according to any one of claims 1 to 3, wherein the controller determines whether the crystallized protein has been collected based on the image data of the imaging device. 5. The manipulation system according to any one of claims 1 to 4, wherein the controller determines whether the crystallized protein has been collected based on the position information. 6. The manipulation system according to any one of claims 1 to 5, wherein the controller determines a predetermined sampling position at which the sampling instrument faces the crystallized protein based on the positional information. 7. The manipulation system according to claim 6, wherein the controller sets a movement route of the sampling instrument from a predetermined initial position to the predetermined sampling position based on the position information. A freezing container containing a freezing liquid and mounted on the sample stage,
8. The manipulation system according to any one of claims 1 to 7, wherein the controller moves the collecting instrument that has collected the crystallized protein to the freezing container, and freezes the crystallized protein with the freezing liquid. A recovery container mounted on the sample stage is provided,
9. The manipulation system according to any one of Claims 1 to 8, wherein the controller moves the collecting instrument from which the crystallized protein has been collected to the collection container, and stores the collecting instrument in the collection container. a container containing a droplet containing the crystallized protein;
a sample stage on which the container is placed;
a collecting instrument that includes a ring-shaped collecting portion at its tip and collects the crystallized protein in a region surrounded by the inner peripheral surface of the collecting portion;
an electric motor for rotating the sampling instrument around a rotation axis orthogonal to the central axis of the sampling part;
an imaging device that images the crystallized protein and the collection instrument;
A method of driving a manipulation system comprising
causing the imaging device to photograph the crystallized protein and the collection device;
a step of detecting position information of the crystallized protein and the collection device based on image data of the crystallized protein and the collection device;
Inside the pickable area, which is an area formed by the trajectory of the inner peripheral surface of the picking portion when the picking instrument linearly moves or rotates around the rotation axis based on the position information, positioning the collection device so that the crystallized protein is located;
The crystallized protein is transferred to the collecting part by linearly moving or rotating the collecting device around the rotation axis so that the crystallized protein passes through the region surrounded by the inner peripheral surface of the collecting part. and
A method of driving a manipulation system including After collecting the crystallized protein, causing the imaging device to photograph the crystallized protein and the collecting instrument again;
determining whether the crystallized protein has been collected based on the image data of the crystallized protein and the collecting device;
11. The method of driving a manipulation system according to claim 10, comprising:

Images