WO2016132399A1 - Cell culture processing equipment - Google Patents

Cell culture processing equipment Download PDF

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Publication number
WO2016132399A1
WO2016132399A1 PCT/JP2015/000803 JP2015000803W WO2016132399A1 WO 2016132399 A1 WO2016132399 A1 WO 2016132399A1 JP 2015000803 W JP2015000803 W JP 2015000803W WO 2016132399 A1 WO2016132399 A1 WO 2016132399A1
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WO
WIPO (PCT)
Prior art keywords
operation
manipulator
unit
operator
culture
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PCT/JP2015/000803
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French (fr)
Japanese (ja)
Inventor
恵市郎 渡辺
和也 古市
Original Assignee
日揮株式会社
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Publication date
Application filed by 日揮株式会社 filed Critical 日揮株式会社
Priority to PCT/JP2015/000803 priority Critical patent/WO2016132399A1/en
Publication of WO2016132399A1 publication Critical patent/WO2016132399A1/en

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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M3/00Tissue, human, animal or plant cell, or virus culture apparatus
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B25HAND TOOLS; PORTABLE POWER-DRIVEN TOOLS; MANIPULATORS
    • B25JMANIPULATORS; CHAMBERS PROVIDED WITH MANIPULATION DEVICES
    • B25J13/00Controls for manipulators
    • B25J13/08Controls for manipulators by means of sensing devices, e.g. viewing or touching devices

Abstract

[Problem] To provide cell culture processing equipment that makes it possible for an operator to achieve correct operation in accordance with a protocol via a manipulator. [Solution] A work chamber 1 is provided with a culture container 26 for culturing cells, a suction tool 22, and an incubator 21. A manipulator 3 within the work chamber 1 is equipped with a movable imaging unit 311 and a tactile function, and said manipulator 3 is remotely operated to perform each of operations relating to the culture container 26 and the suction tool 22. When the manipulator 3 is used to carry out an operation relating to the culturing of cells, a limiting control unit 6 uses a movement limiting unit 71 to limit the movement of an operator P when deviation from movement of the manipulator 3 based on reference movement data 812 stored in advance in a movement storage unit 81 occurs.

Description

Cell culture processing equipment

The present invention relates to a cell culture processing facility provided with a working chamber for processing, processing and culturing cells in regenerative medicine.

In regenerative medicine, for example, human cells are processed, processed, and cultured (hereinafter collectively referred to as “cell culture”) to produce target cells. In order to obtain the target cells, the step of disinfecting the collected cells, the step of isolating the target cells, the step of suspending the isolated cells in the solution, the step of seeding the cells in the solution in the medium, the seeding A series of steps such as a step of culturing cells in a cultured medium and a step of subculture are performed.

Further, each step includes various operations such as adjusting a liquid sample containing cells to a predetermined temperature, adding chemicals to the cells and stirring them, and the operations include processing, processing contents, and target cell. It depends on the type. For this reason, cell culture is performed based on a procedure manual called a protocol that describes the contents of operations performed in each step, thereby improving reproducibility when producing target cells.

However, in cell culture, just because the same operation is performed under the same conditions, the result of each operation is not always the same. For this reason, cell culture in regenerative medicine is largely dependent on the experience and skill of workers, and the effect of skill difference between skilled and unskilled workers on the success and efficiency of cell culture. Is big.

In particular, if an unskilled worker does not fully understand the procedure described in the protocol and performs the wrong operation, it may lead to a situation where valuable cells are wasted. In addition, even a skilled worker may cause an operation error such as skipping a part of the complicated procedure described in the protocol or mistaken operation number during repeated operation. It is difficult to eliminate.

Cited Document 1 discloses an automatic cell culture apparatus in which an articulated robot is disposed in a housing having an opening / closing door on the front side, and a cell culture device is disposed on the back side opposite to the front side. Are listed. However, the cited document 1 does not describe a method of how to realize a correct operation according to a protocol when the operator operates the operation robot.

Reference 2 describes a teleoperator system that drives an end effector that performs treatment of a patient's tissue at a surgical site by operating a controller provided in a remotely located operator control station. . However, the technique described in the cited document 2 does not suggest a technique for realizing a correct operation in a surgical operation realized by an end effector.

Japanese Patent No. 5416919: Claim 1, paragraphs 0018 to 0021, FIGS. Japanese Patent No. 3582777: Claim 1, FIG.

The present invention has been made under such circumstances, and an object thereof is to provide a cell culture processing facility in which an operator operating a manipulator can realize a correct operation according to a protocol. .

The cell culture processing equipment of the present invention includes a culture chamber for cell culture, a suction device for sucking fluid in the culture vessel, and an incubator in which the culture container is housed,
A manipulator that is remotely operated for each of the operations related to cell culture that is an operation on the culture vessel and an operation on the suction tool and is equipped with a movable imaging unit and a tactile function, and provided in the working chamber;
Outside the working room, a monitor unit that displays an image captured by the movable imaging unit, and an operation unit of the manipulator provided with a feedback function that feeds back a haptic perceived by the haptic function attached to an operator When,
An operation restriction unit that is attached to an operator who operates the operation unit and restricts an operation of the operator to operate the operation unit;
An operation storage unit that previously stores reference operation data of the manipulator when an operation related to the culture of the cell is executed by the manipulator;
When the operator performs an operation related to cell culture by the manipulator via the operation unit, the operation of the manipulator based on the operation of the operation unit deviates from the operation of the manipulator based on the reference operation data And a restriction control unit that restricts the operation of the operator by the operation restriction unit.

The cell culture processing facility may have the following features.
(A) The reference motion data stored in advance in the motion storage unit is set based on an operation related to the cell culture performed by the recording target operator wearing the operation unit by the manipulator.
(B) The reference operation data is set for each operation included in a protocol in which a plurality of operation procedures related to cell culture are described.
(C) The reference operation data is set for an operation using a culture container or a suction tool used in the culture operation, and a position where the manipulator is operating the culture container or the suction tool is the reference When the manipulator stored in the operation data is out of the operation region of the culture vessel or the suction tool, the operation restriction unit restricts the operation related to the operation of the operator.
(D) In the operation storage unit, processing operation data of the manipulator when an operation using the culture container or the suction tool is executed is stored in advance, and the manipulator stores the culture container or the suction tool in the operation area. An operation control unit for executing the processing operation of the manipulator based on the processing operation data stored in the operation storage unit instead of the operation of the manipulator by the operator via the operation unit. Having prepared. At this time, the processing operation data stored in advance in the operation storage unit is set based on the processing operation related to the cell culture performed by the recording target operator wearing the operation unit by the manipulator.
(E) The operation unit operates the manipulator based on the movement of the operator's arm, and the operation restriction unit is attached to the operator's arm together with the operation unit, and based on an instruction from the restriction control unit, the operator Restricting the behavior of
(F) The restriction control unit causes the operation restriction unit to operate the operator as the amount of deviation between the manipulator operation based on the operation of the operation unit by the operator and the manipulator operation based on the reference operation data increases. Increase the power to limit.

In the present invention, when the operation of the manipulator operated by the operator outside the work room deviates from the operation based on the reference operation data stored in advance, the operation of the operator is limited using the operation limiting unit. It is possible to realize a correct operation along the line.

It is a cross-sectional top view of the working chamber of the cell culture processing equipment which concerns on embodiment of this invention. It is a vertical side view of the working chamber. It is a perspective view of the manipulator which performs operation in the said working room. It is a front view of the operator who performs remote control of the manipulator. It is a side view of the operator. It is a block diagram of the control part which controls the manipulator. It is explanatory drawing which shows an example of a protocol. It is explanatory drawing which shows the flow of operation implemented based on the said protocol. It is a 1st explanatory view concerning operation of the manipulator. It is the 2nd explanatory view concerning operation of the manipulator. It is a 1st explanatory view showing the processing operation range and standard operation range of the manipulator. It is the 3rd explanatory view concerning operation of the manipulator. It is the 2nd explanatory view showing the processing operation range and standard operation range of the manipulator. It is a flowchart which shows the operation | movement at the time of acquiring the operation data of the said manipulator. It is a 1st flowchart which shows the flow of the operation | movement which implements cell culture based on the said operation | movement data. It is a 2nd flowchart which shows the flow of the operation | movement which implements cell culture based on the said operation | movement data.

Hereinafter, the cell culture processing facility of the present invention, the manipulator 3 for performing various operations in the facility, and the system for controlling the operation thereof will be described with reference to FIGS.
The cell culture processing equipment of the present invention is provided in a work table 2 in which various devices for cell culture are arranged in a work room 1 partitioned from an external atmosphere by a housing 10 and a position facing the work table 2. And a manipulator 3 for executing the operation of the device.

1 and 2, the work table 2 is provided at a height position accessible by a hand 32 of a manipulator 3 described later. In FIG. 1, as an apparatus for cell culture, an incubator 21 for storing a dish 26 as a culture vessel, a pipette device (aspirator) 22 for performing aspiration and supply operations of fluid, and separation of cells dispersed in a liquid sample The example of the work table 2 provided with the centrifuge 23 which performs operation, and the mass culture apparatus 24 which mass-cultivates the target cell culture | cultivated and isolate | separated with the work table 2 is shown.

The incubator 21 includes a shelf that can accommodate a large number of dishes 26 in a housing that can keep the inside at a constant temperature. FIG. 1 shows an example of an incubator 21 in which two rows of front and rear shelves on the front side and the back side are arranged as viewed from the manipulator 3 side. In this case, the dish 26 accommodated in each shelf can be accessed from the near side by configuring the shelf in the front so as to be movable up and down.

The pipette device 22 is used for an operation of sucking a predetermined amount of a liquid sample or various chemicals from a fluid container such as the dish 26 and injecting the liquid sample or various chemicals into another container. The pipette device 22 is detachably held on a stand arranged on the upper surface of the work table 2, for example. Next to a stand for holding the pipette device 22, a plurality of pipette tips 221 configured to be detachable from the pipette device 22 and exchanged according to the fluid to be handled are held by the tip stand 222.

In the centrifuge 23, the centrifuge tube 231 is held in a holder (not shown) of a rotating rotor housed in a casing, and the rotating rotor is rotated to apply centrifugal force to the liquid sample in the centrifuge tube 231 to thereby obtain a liquid sample. Separation of cells inside. Next to the centrifuge 23, a centrifuge tube stand 232 that holds the centrifuge tube 231 is disposed.

The large-scale culture device 24 includes, for example, a culture tank capable of storing a larger volume of culture solution than the cell dish 26, a culture solution stirring device (not shown), and the like. The culture tank is disposed on the lower side of the work table 2, for example, and can be accessed and removed from the outside of the work chamber 1 (the culture tank is indicated by a broken line in FIG. 1). For example, an inlet 241 for injecting the target cells cultured in the dish 26 into the culture tank protrudes from the upper surface of the work table 2. The mass culture apparatus 24 is provided with a culture flask and a flask incubator, but the description is omitted in FIG.

As shown in FIG. 1, a loading / unloading portion 11 for loading / unloading a container or the like containing a sample or a chemical solution to / from the outside is provided on the side wall surface of the housing 10 on the left hand side when viewed from the manipulator 3. ing. The carry-in / out section 11 is a space configured to be freely partitioned from the outside space and the work chamber 1 by the wall surface on the housing 10 side and the opening / closing doors 111 and 112 provided on the work chamber 1 side. Is provided with a loading / unloading stage 113 that is movable with the loaded / unloaded items placed thereon.

Furthermore, the work stage 20 is provided on the work table 2 on the near side of the pipette device 22 and the centrifuge tube stand 232 held on the stand as seen from the manipulator 3 side. The dish 26 operated by the manipulator 3 is placed on the work stage 20. *

In addition, the work table 2 is provided with a transport device 25 configured to be accessible to the work stage 20, the carry-in / out unit 11, and the incubator 21. The transfer device 25 is configured to be able to travel on a traveling rail 251 provided on the work table 2 between the work stage 20 and the carry-in / out unit 11, to be rotatable about a vertical axis, and to be movable up and down. Further, the transport device 25 includes a holding unit 252 that holds an object to be transported such as the dish 26, and the holding unit 252 is expanded and contracted so that the dish on the loading / unloading stage 113 in the loading / unloading unit 11 and the shelves in the incubator 21. 26 holding positions and the work stage 20 can be accessed.

Further, as shown in FIG. 2, a filter unit 12 for filtering gas (for example, air outside the work chamber 1) sent from a fan (not shown) is provided on the ceiling portion of the housing 10 constituting the work chamber 1. It has been. The work chamber 1 is provided with an exhaust unit (not shown) that adjusts the pressure inside the housing 10.

As described above, the cell culture apparatus such as the pipette device 22 that sucks the liquid sample in the dish 26 and the incubator 21 in which the dish 26 is accommodated is separated from the outside by the housing 10. Is provided. And the operation which concerns on the cell culture using these apparatuses is performed using the manipulator 3 arrange | positioned in the working chamber 1. FIG.

As shown in FIG. 3, the manipulator 3 of the present example includes a upper body provided with a head 31 and two arm-shaped hands 32 on a body-shaped hand support portion 36, and is operated by a remote operation. It is configured as a robot.
The head 31 provided at the upper end of the hand support unit 36 includes, for example, two 3D cameras 311, and the direction of the 3D camera 311 can be changed by moving the head 31 up and down and left and right by remote control. The 3D camera 311 and the head 31 correspond to the movable imaging unit of this example. The head 31 is provided with a microphone that detects sound in the work chamber 1.

Each hand 32 includes an arm portion 321 having a plurality of joints and a plurality of, for example, 3 to 5 finger portions 322 provided at the tip of the arm portion 321. Each finger part 322 is provided with a plurality of joints. The movement of the arm portion 321 and the finger portion 322 using each joint is executed by a remote operation described later. Each finger 322 is provided with a pressure sensor (not shown), and a tactile sensation when holding the dish 26 or the like can be fed back to the operator P. In addition, a proximity sensor that detects the proximity of these devices may be provided on the outer surface of the arm portion 321 in order to avoid a collision with the devices in the work chamber 1.

As shown in FIGS. 1 to 3, the hand support portion 36 of the manipulator 3 has a lower surface by a base portion 33 extending in the lateral direction along the work table 2 on which the incubator 21 and the pipette device 22 described above are arranged. Supported from the side. A travel rail 331 is provided on the upper surface of the base portion 33, and the hand support portion 36 (manipulator 3) can move left and right on the base portion 33 along the travel rail 331.
Further, the hand support portion 36 can be freely rotated horizontally on the base portion 33.

On the other hand, two traveling rails 332 are provided on the floor surface of the base portion 33 so as to extend in a direction (front-rear direction) orthogonal to the base portion 33 formed in a horizontally long shape. The base portion 33 is disposed on these traveling rails 332 and can move in a direction toward or away from the work table 2. In FIG. 3, the description of the base portion 33 on the left side is partially omitted toward the drawing.
The base unit 33 is provided with a collision sensor for automatically stopping the movement of the base unit 33 when the manipulator 3 detects an impact that has collided with an obstacle, and a control unit for the drive mechanism of the base unit 33. May be.

The left and right movement operation and turning operation of the hand support portion 36 provided on the base portion 33 and the front and rear movement operation of the base portion 33 are executed by remote control.
The manipulator 3 includes a communication unit (not shown), and the operation signal of the head 31, the hand 32, the hand support unit 36, and the base unit 33 is communicated with the slave side control unit 51 arranged in the work chamber 1. Reception, transmission of image information captured by the 3D camera 311, sound information of the microphone, and pressure information detected by the finger unit 322 are performed. The slave side control unit 51 inputs and outputs these pieces of information with a master side control unit 52 or an automatic control unit 53 (described later) provided on the operation zone side outside the work chamber 1 (shown in FIG. 3). “Signal A, B”). Communication between the manipulator 3 and the slave side control unit 51 may be performed wirelessly or may be performed by wire.

Next, a master system that performs manual operation by the operator P will be described with reference to FIGS. 4 and 5. The operation area of the manipulator 3 in which the master system is provided is not particularly limited as long as it is outside the work room 1. For example, the operation area is provided in a building in which the work room 1 is disposed.

The master system of this example includes a headgear unit 61 mounted on the head of an operator P who performs remote operation of the manipulator 3, a head link mechanism 623 that detects the position and orientation of the headgear unit 61, and both hands of the operator P. A finger link mechanism 621 that is attached to the finger and detects the position and orientation of each finger, and an arm link mechanism 622 that is attached to the hand of the operator P and detects the position and orientation of the arm of the operator P. The head link mechanism 623, the finger link mechanism 621, and the arm link mechanism 622 are attached to the trunk (for example, the back) of the operator P, and the head 31 and the hand 32 in the manipulator 3 (arm part 321 and finger part 322). Is connected to an input / output unit 62 that detects and outputs information that teaches the position and orientation of the input and output.

The movement of the body of the operator P is detected as the amount of change of the joint accompanying the change in shape of the head link mechanism 623, the finger link mechanism 621, and the arm link mechanism 622 (multi-joint structure), and the manipulator 3 is remotely operated. An existing system can be used as a technique for outputting teaching information (operation signal) for the purpose.

The direction of the headgear 61 detected using the head link mechanism 623 is input as an operation signal for changing the direction of the head 31, and the head 31 of the manipulator 3 moves in conjunction with the movement of the head of the operator P. It will be. Further, the operator P is provided with an upper body link mechanism (not shown) that detects a twist around the vertical axis of the upper body, and when the upper body of the operator P is twisted, the hand support portion 36 is horizontally turned toward the twist direction. be able to. Thereafter, when the twist of the upper body of the operator P is returned, the turning of the hand support portion 36 is stopped.
Further, the headgear unit 61 is provided with a 3D monitor that displays an image captured by the 3D camera 311 of the manipulator 3, and the operator P can visually check the inside of the work chamber 1 through the 3D monitor. .

Similarly, the position and orientation of the arm and finger of the operator P detected using the finger link mechanism 621 and the arm link mechanism 622 are input as an operation signal of the hand 32, and the movement of the operator P's arm and finger is taken into account. In conjunction with this, the hand 32 of the manipulator 3 moves. Moreover, the pressure information detected by the pressure sensor of the finger 322 on the manipulator 3 side is transmitted to the glove worn by the operator P as tactile information of an operation for holding the dish 26 by the hand 32, for example.

Further, as shown in FIGS. 4 and 5, this example master system is arranged on a work chair 65 on which an operator P who performs remote control of the manipulator 3 is seated, and on the floor surface under the feet of the operator P seated on the work chair 65. Various operating pedals 631, 632, 641, and 642.

A forward pedal 631 for moving the base portion 33 forward and a reverse pedal 632 for moving backward are provided under the right foot side of the operator P sitting on the work chair 65. On the other hand, a right movement pedal 641 for moving the hand support portion 36 on the base 33 to the right and a left movement pedal 642 for moving to the left are provided on the left foot side of the operator P. Yes. Various corresponding operations are executed during a period in which these operation pedals 631, 632, 641, and 642 are depressed. Moreover, you may comprise so that the moving speed of the base part 33 and the hand support part 36 can be changed according to the depression amount of these operation pedals 631,632,641,642.

The teaching information of the head 31 and the hand 32 acquired from the head link mechanism 623, the finger link mechanism 621, and the arm link mechanism 622 is transmitted to the master side control unit arranged in the operation area via the input / output unit 62. 52 is input. Further, information on the upper body twist of the operator P output from the upper body link mechanism (not shown) and operation information of the operation pedals 631, 632, 641, 642 are also input to the master side control unit 52. These pieces of information are output to the slave side control unit 51 on the work room 1 side as operation signals for remotely operating the manipulator 3. Further, image information, audio information, and pressure information acquired from the slave side control unit 51 are also transmitted to the headgear unit 61 and the glove worn by the operator P via the master side control unit 52.

Here, the head link mechanism 623, the finger link mechanism 621, the arm link mechanism 622, the upper body link mechanism (not shown), the input / output unit 62, and the various operation pedals 631, 632, 641, and 642 described above are manipulators. 3 corresponds to an operation section for transmitting the movement of the operator P to 3 and executing the operation of the device for cell culture.

An operator P that performs remote operation (manual operation) of the manipulator 3 via the master system described above is equipped with an operation restriction mechanism (operation restriction unit) 71 for restricting the operation of the operator P itself.

For example, the motion restriction mechanism 71 is configured as a link mechanism (multi-joint structure) mounted along the arm portion of the operator P whose motion is detected by the arm link mechanism 622. The motion limiting mechanism 71 limits the motion of the operator P by limiting the movement of each joint based on the information input to the input / output unit 62. Since the operation of the manipulator 3 using the arm link mechanism 622 is suppressed by restricting the operation of the operator P, the operation of the manipulator 3 that is not permitted by the operation restricting mechanism 71 is not executed.
The movement restriction mechanism is not limited to the case where the movement restriction mechanism is provided on the arm part of the operator P. The body of the operator P whose movement is detected by the neck part of the operator P whose movement is detected by the head link mechanism 623 and the upper body link mechanism (not shown). It may also be provided in the section.

Under predetermined conditions, the manipulator 3 can automatically execute the operation of the cell culture device based on the processing operation data 813 stored in advance instead of the manual operation by the operator P. .
Hereinafter, a method for executing the operation restriction of the operator P by the operation restriction mechanism 71 and the automatic operation of the manipulator 3 will be described with reference to FIG.

As shown in FIG. 6, the cell culture processing facility of this example includes a control unit 8 including the slave side control unit 51 and the master side control unit 52 described above. For convenience of explanation, FIG. 6 shows the entire control unit 8 including the slave-side control unit 51 and the master-side control unit 52 as a whole.
The control unit 8 is configured as a computer including a CPU (Central Processing Unit) (not shown) and a memory 81. The memory 81 includes a manipulator control program 82 for causing the manipulator 3 to be automatically operated, a restriction mechanism control program 83 for causing the operation restriction mechanism 71 to restrict the operation of the operator P, and the transport device 25 to store the dish 26. A conveyance control program 84 for executing a conveyance operation is stored.
The control unit 8 that operates based on the manipulator control program 82 corresponds to the operation control unit of the present embodiment, and the control unit 8 that operates based on the restriction mechanism control program 83 corresponds to the restriction control unit.

In practice, as described above, the slave-side control unit 51 and the master-side control unit 52 are configured as separate computers, and the slave-side control unit 51 is disposed in the work chamber 1 while the master-side control. The part 52 is arranged on the operation area side where the operator P is located. At this time, the manipulator control program 82 is stored in the memory 81 of the computer common to the slave side control unit 51 in the work room 1, while the restriction mechanism control program 83 is stored in the master side control unit 52 on the operation area side. It is stored in the memory 81 of a common computer.

Further, in the memory 81, the operation of the manipulator 3 is set in advance when the operation data of the operation included in the protocol 4 and the execution order thereof are recorded in advance and the operation restriction of the operator P by the operation restriction mechanism 71 is performed. Reference operation data 812 serving as a reference for determining whether or not there is a deviation from the operation, and processing operation data 813 for executing an automatic operation of the manipulator 3 are stored.

For example, FIG. 7 shows a part of a protocol in which the procedure of the operation performed in the step of peeling the target cell from the bottom surface of the dish 26 in which the target cell is cultured and seeding in the new dish is described.
In the protocol data 811, the operations described in these protocols are broken down into more basic operation units such as “conveying the dish 26 from point A to point B”, “adding Xml of chemical solution to the dish 26”, etc. These are recorded together with the execution order (operation units P1 to P11 in FIG. 8).

By disassembling the operation described in the protocol into operation units, the movable part (for example, each joint part) of the manipulator 3 is in the space constituting the work chamber 1 during the period in which the operation unit is being executed. Correspondence with data indicating the movement trajectory such as from which position to which position can be performed. In addition, since the movable part of the manipulator 3 operates in the work chamber 1 in response to the movement of each link mechanism 621, 622, 623 (operation part), the coordinate position in the work chamber 1 is specified.

As can be seen from the description in FIG. 7, the cell culture operation involves adding a predetermined amount of a specific drug solution to the dish 26 (“Adding X 1 ml of PBS (−)”, “Adding X 2 ml of trypsin”). Etc.) and operations for transporting the dish 26 between specific points (such as “delivering the dish 26 to the transport device 25 from a position above the work stage 20 to which trypsin has been added”). The operation only includes moving the device (such as the dish 26 and the pipette device 22). Such a movement operation is an operation unit that is performed in almost the same way regardless of who the operator P performs.

In the memory 81, data related to the movement trajectory of the movable part of the manipulator 3 in the operation unit related to the movement operation that does not require the judgment of the operator P is stored in advance as the reference operation data 812 for each operation unit. For example, FIG. 8 shows a target operation whose moving trajectory is stored as reference motion data 812, surrounded by a single line. In this respect, the memory 81 corresponds to the operation storage unit of this example.

The control unit 8 that operates based on the restriction mechanism control program 83 includes the position of the movable unit of the manipulator 3 that is manually operated by the operator P and the reference operation data for each preset time interval within the execution period of each operation unit. The movement trajectory of the manipulator 3 stored in 812 is compared. When the movement position of the manipulator 3 that is manually operated is deviated from the movement trajectory, the operation restriction mechanism 71 is operated to restrict the operation of the operator P.

The movement trajectory that is the reference motion data 812 is set based on a result of, for example, a person skilled in the operation as a recording target operator P and the recording target operator P remotely operating the manipulator 3 and executing the operation described in the protocol. The Specifically, the movement trajectory of each movable part of the manipulator 3 executed by the remote operation is recorded.

At this time, in order to prevent the operation restriction mechanism 71 from restricting the operation of the operator P more than necessary, the manual operation by the recording target operator P is repeatedly performed a plurality of times, and a plurality of movement trajectories obtained by these operations are obtained. It is also possible to set the movement trajectory area (movement trajectory area) of the reference motion data 812 so as to include a spatial width. In this case, for example, when the position of the manipulator 3 deviates from the moving track region, the control unit 8 operates the operation limiting mechanism 71 to limit the operation of the operator P.

Further, as another method for preventing the operation of the operator P from being restricted more than necessary by the operation restricting mechanism 71, as the manipulator 3 moves away from the preset movement trajectory (the manipulator 3 by remote operation of the operator P). And the force of the operation limiting mechanism 71 to limit the operation of the operator P may be increased (as the amount of deviation between the above operation and the operation of the manipulator 3 based on the reference operation data 812 increases).

Here, the operations described in the protocol of FIG. 7, such as “add inhibitors when cells are confirmed to be detached ” and “add trypsin when cells are not detached ”, are performed by a 3D camera. Unless the operator P confirms the imaging result in the dish 26 by 311, the next operation unit cannot be determined. In such a case, one of a plurality of preset operation units (operation unit P5 or operation unit P11 in the example of FIG. 8) is selected based on the judgment of the operator P.

For example, after the operation unit P10 (operation for removing the lid of the dish 26) shown in FIG. 8 is executed, either the operation unit P5 for adding trypsin in the dish 26 or the operation unit P11 for adding an inhibitor to the dish 26 is executed. The Therefore, the operation restriction mechanism 71 does not restrict the operation regardless of which of the operation units P5 and P11 is executed. On the other hand, when the manipulator 3 is moved in a direction deviated from the movement trajectory associated with these operation units P5 and P11, the operation restriction mechanism 71 is activated to restrict the operation of the operator P.

Next, a method in which the control unit 8 performs an automatic operation of the manipulator 3 based on the processing operation data 813 will be described.
Here, the operation (operation unit P6 in FIG. 8) such as “trypsin is spread all over the cell” described in the protocol shown in FIG. 7 includes an operation that is difficult for an unskilled operator P to reproduce. It shall be included.

When the contents of the operation unit P6 by a skilled worker are viewed in detail, as shown in FIG. 9, after the dish 26 held by the hand 32 is moved to the upper position of the work stage 20, (a) the dish 26 is moved. (B) an operation for revolving the dish 26 a plurality of times in the counterclockwise direction; (c) an operation for moving the dish 26 a plurality of times in the left-right direction; It is assumed that the operation of moving 26 in the front-rear direction is performed in this order. Even in each of the operations (a) to (d), there are cases where the number of times the dish 26 is moved and the operation speed include subtle tips.

Therefore, some operation units in the protocol data 811 are set so that the manipulator 3 automatically executes a certain operation (indicated by a double line in FIG. 8). In order to realize this automatic operation, the processing operation data 813 stores a movement obtained by the recording target operator P who is an expert in the operation executing the manual operation of the manipulator 3. For example, the recording target operator P manually operates the manipulator 3 and executes the operation (a) of revolving the dish 26 a plurality of times in the clockwise direction. In the processing operation data 813, the movement of the manipulator 3 at this time is recorded in the processing operation data 813 as information indicating the movement trajectory of each movable part and the movement speed at each position on the movement trajectory (operation learning). The example shown in FIGS. 10 and 12 schematically shows the movement trajectory of the position of each joint part (movable part) of the hand 32 in the operations (a) and (d) shown in FIG.

Further, as shown in FIGS. 11 and 13, when the dish 26 is conveyed to a predetermined position by the manipulator 3 in the work chamber 1, the processing operation data 813 is received from a remote operation (manual operation) by the operator P. Switching areas 411 and 412 for switching the operation of the manipulator 3 to the automatic operation based on are set. For example, the switching areas 411 and 412 are set at positions above the work stage 20.

Accordingly, when the manipulator 3 moves along the movement trajectory of the reference operation data 812 and the dish 26 is carried into the switching area 411 in a predetermined operation unit, the processing operation is performed after the operation of the manipulator 3 is switched to the automatic operation. The operation (a) is automatically executed based on the data 813. Thereafter, after a predetermined time elapses, the operation (a) is switched to the operation (b). Then, after the operation (b) is executed for a predetermined time, if the dish 26 is located in the switching area 412, the operations (c) and (d) are executed sequentially.

In these operations, the sense of movement of the dish 26 detected by the pressure sensor of each finger 322 on the manipulator 3 side is transmitted to the glove on the operator P side.
Further, in the operation areas 421 and 422 (set so as to surround the switching areas 411 and 412 described above) indicated by broken lines in FIGS. 11 and 13, the position of the arm of the operator P is the operation areas 421 and 422. When the dish 26 is held outside, the operation restriction mechanism 71 is operated to restrict the operation of the operator P. Accordingly, the operation areas 421 and 422 are also stored in the memory 81 as the reference operation data 812.

Even during the period in which the manipulator 3 is automatically operated, the operator P learns the sense of the operator to operate the dish 26 by feeding back the sense of movement of the dish 26 to the operator P. The degree can be improved.
Here, since the manipulator 3 is disconnected from the operation by the operator P during the automatic operation, the manipulator 3 continues the correct automatic operation even if the arm of the operator P moves greatly, for example. However, in this state, the operator P can not only learn the correct operation feeling, but may also cause an unexpected unintentional movement on the manipulator 3 side when returning to manual operation. Therefore, even during the above-described automatic operation period, when the position of the arm of the operator P deviates from the position corresponding to the state in which the operation of the dish 26 is performed in the operation areas 421 and 422, the operation restriction mechanism 71 causes the operation of the operator P to move. Is limited.

When the skill level of the operator P is improved to a certain level, the operation unit may be executed by manual operation by the operator P instead of automatic operation of the manipulator 3 based on the processing operation data 813. Also in this case, when the operation position of the manipulator 3 related to the manual operation of the operator P is out of the operation areas 421 and 422, the operation of the operator P is limited by the operation limiting mechanism 71, and the correct operation is performed. The operation is corrected to move the dish 26 within the regions 421, 422.

Here, the reference motion data 812 (movement trajectory and motion areas 421 and 422) and the processing motion data 813 set based on the result of manual operation of the manipulator 3 by the recording target operator P are obtained as a result of one manual operation. It is not limited to the case of being determined based on. For example, a series of operations included in the protocol data 811 are repeatedly executed to store data related to each operation, and the reference operation for the best operation unit among the operations related to the individual operation units included in these operations is stored. Data 812 and processing operation data 813 may be selected.

In addition, a series of operations included in the protocol data 811 are repeatedly executed to acquire information on a plurality of operations, and the average of the manipulator 3 realized based on an average value of position data included in these information Various operations may be recorded as the reference operation data 812 and the processing operation data 813.

The operation of the control unit 8 based on the manipulator control program 82 and the restriction mechanism control program 83 described above will be described with reference to FIGS.
FIG. 14 shows a flow of an operation for acquiring reference operation data 812 and processing operation data 813 (hereinafter collectively referred to as operation data), and FIGS. 15 and 16 show the manipulator using these operation data. 3 shows a flow of an operation for executing the operation according to 3.

(Acquisition of operation data)
First, the recording target operator P attaches operation units such as a head link mechanism 623, a finger link mechanism 621, and an arm link mechanism 622, and starts remote operation of the manipulator 3 according to the protocol (FIG. 14). start).

Next, an operation unit Pn for which operation data is acquired is read out from the protocol data 811 executed by the recording target operator P and set (step S101). Other operators that support the acquisition of operation data may perform such a set of operation units, a recording of a moving trajectory described later, and a learning operation switching timing through a touch panel (not shown).

For example, as shown in FIG. 8, with respect to the operation unit P1 of “receiving the dish 26 from the transport device 25”, only the movement trajectory that is the reference motion data 812 is recorded, and the operation subject to motion learning is not included. . In this case (step S102; NO), the movement trajectory of the manipulator 3 is recorded as the reference motion data 812 for the operation in which the manipulator 3 receives the dish 26 from the transport device 25 and transports it above the work stage 20 (step S106). ).
If the operation unit is not the final operation unit (step S107; NO), the next operation unit Pn is set (step S101).

On the other hand, when the operation unit Pn for acquiring motion data includes an operation to be motion learning (step S102; YES), the movement trajectory is recorded (steps S103 and 105) and the motion of the manipulator 3 is recorded. The operation learning (step S104) is executed separately.

For example, in the case of the operation unit P6 described above, the pipette device 22 is returned to the stand from the position after adding a predetermined amount of trypsin to the dish 26 in the preceding operation unit P5, and the hand 32 having the pipette device 22 is moved. Then, the movement trajectory returning to the position in front of the hand support portion 36, for example, which is the position where the operation is finished is recorded (step S103). In the manipulator 3 of this example, the state where the hand 32 is positioned in front of the hand support portion 36 is set to an initial state before starting a predetermined operation or an end state after the operation is ended. Yes.

Next, the operations (a) to (d) described with reference to FIGS. 9 to 13 are sequentially executed, and the movement trajectory of the movable part of the hand 32 and the movement speed at each position on the movement trajectory in these operations. Is recorded as processing operation data 813 (step S104). In addition, the areas where this operation is performed are recorded as switching areas 411 and 412, and the operation areas 421 and 422 are set so as to include the switching areas 411 and 412 and recorded.
Thereafter, after the operation is completed, the movement trajectory of the operation of moving the dish 26 to the standby position above the work stage 20 with the dish 26 held is recorded (step S105).

In this way, for each operation unit Pn set in the protocol data 811, the standard operation data 812 is sequentially recorded, and when the operation data related to the last operation unit is acquired (step S107; YES), the manipulator by the recording target operator P 3 remote control is finished.

Here, for example, when different operations are selected depending on the state of the target cell in the dish 26, the operation shown in FIG. 14 is repeated a plurality of times, and both of the different operations are executed. The movement trajectory of the operation can be recorded (for example, when the operation unit P10 → P5 in FIG. 8 is executed and when the operation unit P10 → P11 is executed).
If there is an operation unit with a low probability of being selected, the result of separately recording the movement trajectory may be recorded as the reference motion data 812 separately.

(Operation execution by manipulator 3)
The operator P wears operation units such as the head link mechanism 623, the finger link mechanism 621, and the arm link mechanism 622, and starts remote operation (start in FIG. 15).

The controller 8 reads the operation unit Pn from the protocol data 811 (step S201), and reads the reference operation data 812 and the processing operation data 813 recorded in association with the operation unit Pn.

If the read operation unit Pn is not associated with the learned processing operation data 813 (step S202; NO), whether or not the manipulator 3 is moving along the movement trajectory that is the reference operation data 812. Is confirmed (step S204).
As a result, when the position of the manipulator 3 is deviated from the movement trajectory (step S204; NO), the operation restriction mechanism 71 is operated to restrict the operation of the operator P (step S205).

On the other hand, when the position of the manipulator 3 is along the movement trajectory (step S204; YES), the operation of the manipulator 3 based on the manual operation of the operator P is continued (step S206). In order to simplify the description, FIG. 15 shows the operations related to steps S204 to S205 in one loop, but these operations are performed for a predetermined time during the period until each operation unit Pn is completed. It is repeated at intervals (the same applies to steps S301 to S302 and S309 to 310 in FIG. 16).

On the other hand, when the learned processing operation data 813 is associated with the read operation unit Pn (step S202; YES), the operation shown in FIG. 16 is executed (step S203).

That is, it is confirmed whether the position of the manipulator 3 is along the movement trajectory (step S301 in FIG. 16), and when it is deviated from the movement trajectory (step S301; NO), the operation restriction mechanism 71 is operated to operate the operator. The operation of P is limited (step S302).

If the position of the manipulator 3 is along the movement trajectory (step S301; YES), the operation of the manipulator 3 based on the manual operation of the operator P is continued (step S303). Then, the operation target (for example, the dish 26) is conveyed until the switching areas 411 and 412 are reached (step S304; NO, S303). When the operation target is located in the switching areas 411 and 412 (step S304; YES), the manipulator 3 is switched to automatic operation, and the manipulator 3 is automatically operated based on the learned processing operation data 813 (step S306).

When the position of the arm on the operator P side is out of the operation areas 421 and 422 during the period of performing the operation (step S306; NO), the operation restriction by the operation restriction mechanism 71 is executed (step S307). . These operations are repeated until a preset time has elapsed (steps S305 to S308; NO).

Thus, when the automatic operation is executed for a predetermined time (step S308; YES), the manipulator 3 is switched to the manual operation by the operator P, and it is confirmed whether or not the position is along the moving track (step S309). Accordingly, the operation restriction mechanism 71 restricts the operation of the operator P (step S310), and the manipulator 3 is operated to a position where the operation of the next operation unit Pn + 1 is started (step S311).

Returning to the description of FIG. 15, the operation of the manipulator 3 using the reference operation data 812 and the processing operation data 813 described above is repeated for each operation unit Pn recorded in the protocol data 811 (steps S201 to S207; NO), when the final operation unit is completed, the cell culture operation described in the protocol is finished (END).

The cell culture processing facility according to the present embodiment has the following effects. When the operation of the manipulator 3 operated by the operator P outside the work chamber 1 deviates from the operation based on the pre-stored reference operation data 812 (data indicating the movement trajectory and the operation areas 421 and 422), the operation restriction mechanism 71 is used to restrict the operation of the operator P, so that a correct operation along the reference operation data 812 can be realized.

In addition, by executing the operation in the work chamber 1 via the manipulator 3, it is possible to perform a powerful sterilization operation that is difficult to perform in a space in which a person usually enters, a sterilization process using a medicine in the entire work chamber 1, and the like.
Furthermore, since there is no direct operation by human beings as the largest contamination source, it is possible to surely prevent microbial contamination.

Here, in the above-described embodiment, as an example of the automatic operation based on the processing operation data 813, the operation of moving the dish 26 to spread trypsin over the entire cell (FIGS. 9 to 13) has been described. It is not limited to this.

For example, “shake the medium in the dish 26 so as not to touch the lid ”, “lift the dish 26 while confirming that not only the lid but also the body of the dish 26 is touching ”, “ the side of the dish 26 “Aspirate the cell suspension without touching the pipette tip 221 to the bottom surface ”, “Distribute the cell suspension uniformly throughout the dish 26 while shaking the dish 26 back and forth without rotating the dish 26”, “ Pipette tip The tip of 221 is positioned very close to the liquid surface, and the liquid in the centrifuge tube stand 232 is sucked ”,“ the cell suspension sucked by the pipette device 22 is divided into a plurality of dishes 26 as soon as possible ”, etc. By recording the processing operation data 813 for various operations that require experience of a skilled person, it is difficult for the unskilled person to reproduce. It is possible to perform gastric operation automatically.

Also, the configuration of the operation restriction unit that restricts the operation of the operator P based on the reference operation data 812 is not limited to the example of the multi-joint structure shown in FIGS. For example, a lever is provided that extends from a base end provided on the ceiling or floor of the operation area where the operator P is operating, and whose end is connected to a joint such as an elbow or wrist of the operator P. It may be a limiting unit. In this case, when the operation is not restricted, the lever moves following the movement of the elbow or wrist of the operator P, and when the operation is restricted, the movement of the lever is stopped to restrict the movement of the operator P's elbow or wrist. .

Furthermore, a method for determining whether or not the operation limiting unit (the control unit 8 that operates based on the limiting mechanism control program 83) operates the operation limiting mechanism 71 to limit the operation of the operator P is that of the movable unit of the manipulator 3. The present invention is not limited to the case where the position is determined based on whether or not the position deviates from the predetermined movement trajectory region. For example, when the actual moving direction of the movable part is deviated by a predetermined angle or more from the direction along the moving track as compared to a preset moving track, the operation of the operator P is limited. It is good.

Furthermore, the cells cultured in the cell culture processing facility of this example are not limited to human cells, and may be animal cells, plant cells, or single-cell organism cells.

P Operator 1 Work room 2 Work table 21 Incubator 22 Pipette device 26 Dish 3 Manipulator 311 3D camera 32 Hands 411 and 412
Switching area 421, 422
Operation area 51 Slave side control section 52 Master side control section 61 Head gear section 621 Finger link mechanism 622 Arm link mechanism 623 Head link mechanism 71 Operation restriction mechanism (motion restriction section)
8 Control unit 81 Memory 811 Protocol data 812 Reference operation data 813 Processing operation data 82 Manipulator control program 83 Restriction mechanism control program 84 Transport control program

Claims (8)

  1. A working chamber comprising a culture vessel for cell culture, a suction tool for sucking fluid in the culture vessel, and an incubator in which the culture vessel is stored;
    A manipulator that is remotely operated for each of the operations related to cell culture that is an operation on the culture vessel and an operation on the suction tool and is equipped with a movable imaging unit and a tactile function, and provided in the working chamber;
    Outside the working room, a monitor unit that displays an image captured by the movable imaging unit, and an operation unit of the manipulator provided with a feedback function that feeds back a haptic perceived by the haptic function attached to an operator When,
    An operation restriction unit that is attached to an operator who operates the operation unit and restricts an operation of the operator to operate the operation unit;
    An operation storage unit that previously stores reference operation data of the manipulator when an operation related to the culture of the cell is executed by the manipulator;
    When the operator performs an operation related to cell culture by the manipulator via the operation unit, the operation of the manipulator based on the operation of the operation unit deviates from the operation of the manipulator based on the reference operation data And a restriction control unit that restricts the operation of the operator by the operation restriction unit.
  2. The reference motion data stored in advance in the motion storage unit is set based on an operation related to culture of the cell performed by a recording target operator wearing the operation unit by a manipulator. 2. The cell culture processing facility according to 1.
  3. 2. The cell culture processing facility according to claim 1, wherein the reference operation data is set for each operation included in a protocol in which a plurality of operation procedures related to cell culture are described.
  4. The reference operation data is set for an operation using a culture container or a suction tool used in the culture operation, and a position where the manipulator is operating the culture container or the suction tool is the reference operation data. 2. The cell according to claim 1, wherein an operation related to an operator's operation is limited by the operation limiting unit when the cell is out of an operation area of a culture vessel or a suction device stored in advance by a manipulator. Culture processing equipment.
  5. The operation storage unit stores in advance processing operation data of the manipulator when an operation using the culture vessel or the suction tool is executed,
    When the manipulator moves the culture vessel or the suction tool into the operation area, the manipulator is operated based on the processing operation data stored in the operation storage unit instead of the operation of the manipulator by the operator via the operation unit. The cell culture processing facility according to claim 1, further comprising: an operation control unit that executes a processing operation of the manipulator.
  6. The processing operation data stored in advance in the operation storage unit is set based on a processing operation related to cell culture performed by a recording target operator wearing the monitor unit and the operation unit by a manipulator. The cell culture processing facility according to claim 5.
  7. The operation unit operates the manipulator based on the movement of the arm of the operator, and the operation restriction unit is attached to the operator's arm together with the operation unit and performs the operation of the operator based on an instruction from the restriction control unit. The cell culture processing facility according to claim 1, wherein the cell culture processing facility is limited.
  8. The restriction control unit is a force that restricts the operation of the operator by the operation restriction unit as a deviation amount between the manipulator operation based on the operation of the operation unit by the operator and the manipulator operation based on the reference operation data increases. The cell culture processing equipment according to claim 1, wherein


PCT/JP2015/000803 2015-02-19 2015-02-19 Cell culture processing equipment WO2016132399A1 (en)

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