JP6472868B2 - Cell culture processing equipment - Google Patents

Description

  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, the operator who performs actual operation needs to adjust the content of the operation performed next according to the result of each operation, according to a protocol. In addition, it is difficult to describe the details of each operation in the protocol, such as operations that do not give excessive physical shock to the cells and handling that does not destroy the cultured cell mass. Many.

  For this reason, cell culture in regenerative medicine is largely dependent on the experience and skill of workers, and the skill difference between skilled and unskilled workers gives success or efficiency to cell culture. A large impact. Moreover, the point which requires various adjustments according to the progress of cell culture is a factor that makes it difficult to automate cell culture.

  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. Have been described. However, in the cited document 1, there is no description of how to realize the operation of a skilled worker by 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, also in the technique described in the cited document 2, the surgical operation realized by the end effector changes depending on the skill of the operator who performs the operation of the controller. For this reason, the technique which supplements the skill of the unskilled person in cell culture is not suggested.

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 capable of reproducing the skill of an expert.

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 operation on the culture vessel and the operation on the suction tool and is equipped with a movable imaging unit and a tactile function, and provided in the work chamber;
A communication unit that transmits image information of an image captured by the movable imaging unit to a monitor worn by an operator, and transmits pressure information obtained by a tactile function of the manipulator to a glove worn by the operator;
A memory that is provided outside the work chamber and stores operation data of the manipulator as teaching data when an operation on at least one of the culture vessel and the suction tool is executed by the manipulator by an operation unit that transmits the movement of the operator. And
And a control unit for reading the teaching data and causing the manipulator to automatically execute at least one of the culture vessel and the suction tool.

The cell culture processing facility may have the following features.
(A) A plurality of the teaching data is prepared in accordance with a state of an operation target for at least one of the culture vessel and the suction tool, and the movable type mounted on the manipulator from the plurality of teaching data. Teaching data selected based on an image obtained by the imaging unit is used.
(B) A manual selection selection unit is provided for an operator to select teaching data to be used from the plurality of teaching data based on the image obtained by the movable imaging unit in (a). Was it. In addition, a selection unit for automatic selection for automatically selecting teaching data to be used from the plurality of teaching data based on an image obtained by the movable imaging unit is provided.
(C) a switching unit that switches whether the operator's movement is “valid” or “invalid” with respect to the remote operation, and after being switched to “invalid” by the switching unit, The manipulator is configured to automatically execute the operation from a predetermined initial state based on teaching data read from the memory. At this time, the control unit is configured to return to the initial state after the manipulator automatically executes the operation.

  The present invention provides an operation unit that is provided outside a work chamber and that transmits an operator's movement when at least one of the culture vessel for cell culture and the suction tool is operated by the manipulator provided in the work chamber. Since the operation data is stored as teaching data, the operation can be automatically controlled.

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 operation performed by the said manipulator. It is a selection screen for selecting target operation which accumulate | stores the teaching data of the said manipulator. It is a selection screen for selecting object operation which performs automatic operation with the manipulator. It is a flowchart which shows the flow of the operation | movement which accumulate | stores the said teaching data. It is a flowchart which shows the flow of the operation | movement which performs the said automatic operation.

Hereinafter, the cell culture processing facility of the present invention, the manipulator 3 that performs various operations in the facility, and the system that controls 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.

  As shown in FIGS. 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 capable of keeping 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 mass 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.

  Further, a 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 by the stand as viewed from the manipulator 3 side. The dish 26 operated by the manipulator 3 is placed on the work stage 20.

  Further, the work table 2 is provided with a transfer 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 the dish 26 is held 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 base portion 33 that extends laterally 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.
In addition, the hand support portion 36 can freely turn 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.

Furthermore, the manipulator 3 can switch and execute a remote operation (manual operation) by the operator P via the master-side control unit 52 and an automatic operation based on teaching data stored in advance.
First, a master system that performs a 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 on 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.

The manipulator 3 that is remotely operated (manually operated) via the master system described above has the operation data of the operation executed by the manual operation (the head 31 at each time in the period of executing the operation, According to the position data of the hand support part 36, the hand 32 (arm part 321 and finger part 322) and the base part 33, the moving speed data at each position specified by the position data, the force applied to the dish 26 and the pipette device 22. By storing pressure data, etc.) as teaching data, the operation of the cell culture device can be automatically executed based on the teaching data.
As a result, the skilled person performs manual operation of the manipulator 3 using the master system described above in advance, and the skill data of the skilled person is automatically obtained by using the operation data of the manipulator 3 at that time as teaching data. It can be reproduced.

In order to acquire the above-mentioned teaching data, as shown in FIG. 6, the cell culture processing equipment of this example includes a control unit (automatic control unit 53) for automatically executing the operation of the device for cell culture by the manipulator 3. A switching unit 54 that switches between a valid state / invalid state of manual operation using the master system and a touch panel 7 that receives instructions from the operator P related to storage of teaching data and execution of automatic operations are provided.
For convenience of explanation, FIG. 6 shows the entire control unit 50 including the automatic control unit 53, the slave-side control unit 51, and the master-side control unit 52 described above.

  The control unit 50 is configured as a computer including a CPU (Central Processing Unit) and a memory (storage unit) 501 (not shown), and the memory 501 stores teaching data for executing the automatic operation of the manipulator 3. . The teaching data is stored in the memory 501 of the control unit 50 for each operation of each device for cell culture or for each group of operations.

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, while the master-side control unit 52 is configured. Is arranged on the operation area side where the operator P is located.
The automatic control unit 53 plays a role of performing automatic operation of the manipulator 3 based on the teaching data by switching to manual operation using the slave side control unit 51 and the master side control unit 52. For example, the automatic control unit 53 is configured by a computer common to the slave side control unit 51.

  The automatic operation executed based on each teaching data starts from an initial state and ends in an end state after a series of operations. The initial state is, for example, a state in which the hand 32 of the manipulator 3 has nothing and the left and right hands 32 are aligned in front of the hand support portion 36. The end state is set to the same state as the initial state, for example. The initial state (end state) is set to the so-called origin position of the hand 32.

  Here, a case will be described in which, among a series of operations described in the protocol performed in cell culture, for example, only a part of the operations is switched to an automatic operation using teaching data. At this time, when the next operation is performed automatically after the manual operation of the manipulator 3, the hand 32 of the manipulator 3 is first set to the initial state from the end state of the preceding operation, and from the initial state to the next state. The operation starts and ends (same as the initial state). Further, when the next operation is performed manually, the work starts from this end state. That is, the teaching data is configured as operation data until the hand 32 starts from the initial state and returns to the same state.

  As described above, the manual operation is performed while reflecting the result of the pressure information detected by the finger part 322 on the hand 32 side being transmitted to the glove of the operator P as tactile information. For this reason, the motion data is also based on the result of feedback of the tactile information, and the delicate motion obtained as a result of the manual operation by the operator P based on the tactile information is stored. Yes.

  As described above, the operation by the hand 32 in the work chamber 1 can be imaged by the movable 3D camera 311 mounted on the head 31 provided at the upper end of the hand support portion 36. The operator P can see the image from the 3D camera 311 by the 3D monitor of the headgear unit 61 mounted on the head.

For example, a plurality of teaching data is prepared for each state of an operation target (operation target ) that is an automatic operation target. Therefore, when the automatic operation is performed, the operator P provides teaching data corresponding to the captured image of the 3D camera 311, specifically teaching data corresponding to the state of the operation object recognized from the captured image of the 3D camera 311, Selection can be made via a screen displayed on the touch panel 7. For example, the 3D monitor of the headgear unit 61 is translucent or the field of view of the line of sight is transparent, and both the image of the 3D monitor and the screen displayed on the touch panel 7 can be viewed.

  The teaching data prepared according to the state of the object to be operated has a variation when the state of the object to be operated (for example, the size of the cell mass in the dish 26 or the state of cell dispersion in the liquid sample) tends to vary. A plurality of operations are prepared in advance so that operations associated with the respective states can be performed.

  Here, as a method for selecting an operation to be executed from a plurality of teaching data during the automatic operation, for example, based on the recognition result of the captured image of the 3D camera 311, the automatic control unit 53 that performs the automatic operation of the manipulator 3, for example, Teaching data corresponding to the state of the operation target may be selected by image matching or the like. In this case, the automatic control unit 53 constitutes a selection unit for automatic selection of teaching data Dn (n = 1, 2,...).

Further, when it is time to select the teaching data, the automatic operation of the manipulator 3 may be stopped, and the teaching data may be selected from the operation screen of the touch panel 7 based on the result of the operator P confirming the 3D monitor image. . Further, depending on whether or not automatic determination such as image matching is easy, the method in which the operator P selects teaching data and the method in which the automatic control unit 53 selects teaching data may be used.
Therefore, in the automatic operation of the manipulator 3, the captured image of the 3D camera 311 is used when the operator P selects teaching data or when the automatic control unit 53 automatically selects teaching data.

  Further, as shown in FIG. 6, the automatic control unit 53 is connected to a switching unit 54 that performs switching between a valid / invalid state of manual operation. For example, the switching unit 54 is configured as a pedal provided on the outer side of the forward and backward pedals 631 and 632 described above at the foot of the operator P (FIG. 4). At this time, the pedal constituting the switching unit 54 is provided with a stopper that maintains the state where the pedal is lowered once depressed, and returns to the original position when depressed again. Thus, by switching between the state where the pedal is lowered and the state where the pedal is returned to the original position, the valid / invalid state of the manual operation is switched.

The operation of the cell culture processing facility having the configuration described above will be described.
Hereinafter, after culturing the target cells seeded in the medium in the dish 26 in the incubator 21, the target cells are detached from the dish 26 to prepare a cell suspension and seeded in a new dish 26. The operation will be described as an example.

As a specific example, after adding trypsin to the dish 26 in which the target cells are cultured, the target cells peeled off from the bottom surface of the dish 26 are collected again for the dish 26 held in the incubator 21 for a new dish 26. The operation of sowing the seed will be described.
In this operation, an operation of accumulating teaching data when the operator P manually operates the manipulator 3 and an operation of executing an automatic operation using the teaching data will be sequentially described.

(Accumulating teaching data)
The operator P wears the headgear unit 61, the glove, and the input / output unit 62, sits on the work chair 65, switches the switching unit 54 to a state where manual operation is effective, and starts manual operation of the manipulator 3. As an operator P that executes an operation stored as teaching data, for example, an operator skilled in the operation is selected.

  First, after the addition of trypsin, the transport device 25 takes out the dish 26 a held for a predetermined time in the incubator 21, transports it, and places it on the work stage 20. Next, before starting to store the teaching data, an image of the dish 26 a is taken via the 3D camera 311, and information regarding the cell dispersion state in the dish 26 a is stored in the master-side control unit 52. In this operation, for example, the dish 26a on the work stage 20 is lifted and then tilted, and the state of attachment of cells attached to the bottom surface of the dish 26a is also imaged.

  Here, as the information regarding the dispersion state of the cells, the degree of dispersion may be selected from n types of classification information (for example, “good”, “slightly good”, “bad”, etc.) and associated with the image data. it can. The association of the classification information is performed based on the experience of the operator P, for example. Thereby, the teaching data acquired from this and the image data of the dispersed state of the cells in the dish 26a are associated with each other through the classification information and stored in the memory 501.

  Next, the operator P places the dish 26a on the work stage 20, and moves the hand 32 of the manipulator 3 to the initial position (step S11 in FIG. 10). Thereafter, the operator P switches the manual operation of the manipulator 3 to the invalid state by the switching unit 54 (step S12). Next, the operator P selects “cell suspension preparation operation” from the data accumulation menu 711 on the data accumulation operation selection screen 71 displayed on the touch panel 7 and presses “start” of the start / end switch button 712. (Step S13, FIG. 8). Subsequently, the operator P switches the manual operation of the manipulator 3 to the valid state by the switching unit 54 (step S14), and performs a series of manual operations related to the cell suspension preparation operation on the manipulator 3 waiting at the initial position. Execute (Step S15).

Specifically, after attaching a predetermined pipette tip 221 to the pipette device 22, the pipette device 22 is gripped by the right hand 32, and a cell dispersion medium is aspirated from a predetermined drug solution container, A preparatory operation for dividing a predetermined amount of culture solution into two new dishes 26b and 26c is performed.
Next, the trypsin-treated dish 26 placed on the work stage 20 is grasped with the left hand, and the culture solution in the dish 22b is sucked by the pipette device 22 and then injected into the dish 26a. At this time, the pipette device 22 is operated so that the dish 26a is tilted and the cells adhering to the bottom are peeled off.

  Further, the cell suspension accumulated in the lower part of the tilted dish 26 is again sucked by the pipette device 22 and injected into a high part (surface without liquid) at the bottom of the tilted dish 26 to further detach the cells. (FIG. 7A). After repeating such an operation a plurality of times, the culture solution is aspirated by the pipette device 22 from the above-described dish 26c containing the culture solution for diluting the cell suspension and injected into the dish 26a (FIG. 7). (B)).

  Thereafter, the pipette device 22 is returned to the stand, and then the dish 26a is moved to stir the liquid. For example, the dish 26a is revolved clockwise several times, then revolved counterclockwise several times, further swung left and right several times, and finally shaken up and down several times (FIG. 7C).

  Thereafter, when the dish 26 a is placed on the work stage 20, the dish 26 a is transported into the incubator 21 by the transport device 25. The operator P sets the hand 32 of the manipulator 3 to the end state. The end state is the same as the initial state, for example. Thereafter, the operator P switches the manual operation of the manipulator 3 to an invalid state by the switching unit 54 and presses the “end” button of the start / end switch button 712 via the data storage operation selection screen 71. As a result, operation data of important operations related to the subculture process of the target cell is stored in the memory 501 as teaching data.

(Switch to automatic operation)
For example, the operator P who is an unskilled worker manually operates the manipulator 3 using the master system, is taken out of the incubator 21 by the transport device 25, and is placed on the work stage 20 after the trypsin processing dish. Take 26a. Then, the image of the dish 26a is picked up by the 3D camera 311. After obtaining information on the cell dispersion state in the dish 26a, the dish 26a is placed on the work stage 20 again.

  Next, the operator P switches the manual operation of the manipulator 3 to an invalid state by the switching unit 54 (step S21 in FIG. 11), and the “cell floating” in the operation selection button 721 is displayed via the automatic operation selection screen 72 displayed on the touch panel 7. “Liquid creation operation” is selected (step S22, FIG. 9). In addition, based on the image of the dish 26a displayed on the 3D monitor of the headgear unit 61, the dispersion state of the cells in the dish 26a (pattern) can be selected from the pattern selection button 731 on the pattern selection screen 73 displayed following the automatic operation selection screen 72. Data (teaching data Dn) corresponding to Pn) is selected (step S23, FIG. 9). Here, the pattern selection screen 73 of FIG. 9 shows an example in which the teaching data D1 to D3 can be selected corresponding to the three types of patterns P1 to P3. As described above, the teaching data Dn may be automatically selected by the automatic control unit 53 by image matching or the like.

After that, when “Start” is pressed with the start / end switching button 722 on the automatic operation selection screen 72 displayed on the touch panel 7, the selected teaching data Dn is read, and the manipulator 3 is automatically operated based on the read teaching data. The operation is executed (step S24).
That is, the manipulator 3 is first in an initial state before the cell suspension preparation operation. Then, the manipulator 3 reproduces a series of cell suspension preparation operations performed by an expert performed when teaching data is accumulated (step S25).

  Thereafter, when the cell suspension preparation operation is completed, the manipulator 3 is in an end state (step S26). In this example, the operator P switches the manual operation of the manipulator 3 to the valid state by the switching unit 54 (step S27), and executes the subsequent operation by manual operation (step S28).

  Here, in step S25 for reproducing the cell suspension preparation operation, when the operation of peeling the cells of the dish 26a is repeatedly performed (FIG. 7A), based on the image of the dish 26a displayed on the 3D monitor, Data (teaching data Dn) corresponding to the cell dispersion state (pattern Pn) in the dish 26a may be selected from the pattern selection button 731 on the pattern selection screen 73 each time it is repeated. In this case, for example, a predetermined state in the repetitive operation, for example, a state where the pipette device 22 is slightly separated from the dish 26a is set as an initial state, and the pipette device 22 is moved again to the same position after the peeling operation is completed. The state is the end state. Thereafter, based on the image of the dish 26a, it is selected whether to repeatedly perform the cell detachment operation or to perform the subsequent cell suspension dilution operation.

  The cell culture processing facility according to the present embodiment has the following effects. An operation unit (a head link mechanism 623, a finger link mechanism 621, an arm link mechanism 622, an upper body link mechanism (not shown), an input / output unit 62, and the like provided on the outside of the work chamber 1 to transmit the movement of the operator P. When the operation pedal 631, 632, 641, 642) is operated to operate at least one of the cell culture dish 26 and the incubator 21 by the manipulator 3 provided in the work chamber 1, the operation data of the manipulator 3 is taught. Since it is stored as data, the operation can be automatically controlled.

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, a part of operations in the passaging process of the target cell is exemplified to explain a technique for accumulating teaching data and an operation for executing an automatic operation of the manipulator 3 by using the accumulated teaching data. Went.
However, it is needless to say that the accumulation of teaching data and the operation target automatically executed based on the teaching data are not limited to the illustrated operations.

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 231 is sucked ”,“ the cell suspension sucked by the pipette device 22 is divided into a plurality of dishes 26 as soon as possible ”, etc. Accumulation of teaching data on various operations that require experience of a skilled person makes it difficult to describe in the protocol. It is possible to automatically execute the operation of the person.

  Further, the method of accumulating teaching data is not limited to the case where one manual operation of the manipulator 3 by the operator P is stored. For example, a series of target operations are repeatedly executed to store operation data for each operation, and the best operation is selected from the operation data related to individual operations included in these operations. Teaching data may be configured by connecting operation data.

  In addition, an average of the manipulator 3 realized based on an average value of position data, pressure data, and the like included in these operation data is obtained by repeatedly executing a target series of operations. The operation may be teaching data.

  Furthermore, the cells cultured in the cell culture processing facility of this example are not limited to human cells, but 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 hand 51 slave side control unit 52 master side control unit 53 automatic control unit 501 memory 54 switching unit 61 headgear unit 621 finger link mechanism 622 Arm link mechanism 623 Head link mechanism 631 Forward pedal 632 Reverse pedal 641 Right movement pedal 642 Left movement pedal 7 Touch panel

Claims (6)

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 operation on the culture vessel and the operation on the suction tool and is equipped with a movable imaging unit and a tactile function, and provided in the work chamber;
A communication unit that transmits image information of an image captured by the movable imaging unit to a monitor worn by an operator, and transmits pressure information obtained by a tactile function of the manipulator to a glove worn by the operator;
A memory that is provided outside the work chamber and stores operation data of the manipulator as teaching data when an operation on at least one of the culture vessel and the suction tool is executed by the manipulator by an operation unit that transmits the movement of the operator. And
A cell culture processing facility, comprising: a control unit for reading the teaching data and causing the manipulator to automatically execute at least one of the culture container and the suction tool. A plurality of the teaching data is prepared according to the state of the operation target for at least one of the culture vessel and the suction tool,
The cell culture processing according to claim 1, wherein teaching data selected from a plurality of the teaching data based on an image obtained by the movable imaging unit attached to the manipulator is used. Facility.   A manual selection selection unit is provided for allowing an operator to select teaching data to be used from among the plurality of teaching data based on an image obtained by the movable imaging unit. Item 3. The cell culture processing facility according to Item 2.   The control unit includes a selection unit for automatic selection for automatically selecting teaching data to be used from the plurality of teaching data based on an image obtained by the movable imaging unit. The cell culture processing facility according to claim 2. A switching unit for switching whether the operator's movement is "valid" or "invalid" for the remote operation;
After being switched to “invalid” by the switching unit, the control unit automatically executes the operation from a predetermined initial state based on teaching data read from the memory. The cell culture processing facility according to claim 1, wherein the cell culture processing facility is configured.   6. The cell culture processing facility according to claim 5, wherein the control unit is configured to return to the initial state after the manipulator automatically executes the operation.

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