WO2013145283A1

WO2013145283A1 - Cell culture device, control device, and method

Info

Publication number: WO2013145283A1
Application number: PCT/JP2012/058653
Authority: WO
Inventors: 豊茂小林; 亮太中嶌; 貴之野崎; 志津松岡; 直子千田
Original assignee: 株式会社日立製作所
Priority date: 2012-03-30
Filing date: 2012-03-30
Publication date: 2013-10-03
Also published as: JPWO2013145283A1; JP5905078B2

Abstract

Screens which must needs be operated in inputting, selecting, and changing a culture schedule increase, a demand of an operator grows, and processes such as approving changes become complicated. In the present invention, a separation is made between a culture scheduling software (15) for culture scheduling management, and an auto-culture control software (12), and a communication (31) is carried out therebetween. The culture scheduling software (15) minimizes scheduling change processes from an operator's input work or cellular culture prediction for culture schedule creation by a GUI, eliminating input errors and making a console operation easy. The auto-culture control software (12) runs in the background, and controls, by the communication with the culture scheduling software (15), hardware (33) for culturing of a vital tissue. If the culture scheduling software (15) fails, administrating on the auto-culture control software (12) side allows stabilizing the quality of the produced vital tissue.

Description

Cell culture device, control device, and method

The present invention relates to a cell culture apparatus for culturing cells, and more particularly to a technique for optimizing the operation of the cell culture apparatus by selecting an efficient culture method from the state of the cells.

In recent years, regenerative tissues that have been reconstructed into biological tissues having a partial function of internal organs by culturing cells outside the body have been actively developed. Among them, regenerative medicine treats a diseased or deficient organ with a regenerative tissue. In particular, skin, cartilage, cornea, etc. are used for treatment all over the world and are becoming common medical care. In addition, since the regenerated tissue has some or all functions of internal organs, it may be used in tests for evaluating the effects of drugs and the like. For example, cultured skin epithelium has already been put to practical use in drug effect tests such as cosmetics and transdermal drugs.

Although the regenerative organization is spreading in this way, its production is carried out manually by skilled workers under strict processes. For this reason, when producing regenerated tissue, the time and cost required to educate and train workers for quality stability, human error, and biological contamination by humans with bacteria etc. (contamination) ) Is costly. Therefore, it is expected that these problems can be solved by automating a series of culture operations using an instrument.

Currently, in manual culture, cell culture processing such as medium exchange is performed in accordance with the culture process defined in the standard procedure manual. However, cells undergo the same culture treatment, and their proliferation and change are often not the same and easily change due to uncertain factors. Therefore, culture treatment according to the state of the cell must be performed. Therefore, as the culture process proceeds, the state of the cultured cells is observed with a phase-contrast microscope, etc., and the culture process is changed based on the experience of the operator due to its shape and growth condition. There is. Currently, in automatic culture, an automatic culture schedule is set based on a culture process defined for manual work, and the automatic culture process is performed by incorporating the schedule into an automatic culture apparatus. Therefore, the operator needs to easily create, modify, and select an automatic culture schedule before the start of the automatic culture process depending on the state of the cells. Furthermore, for example, in medium exchange, the processing time is usually fixed in the culture process, and in order to change the medium exchange processing time according to the state of the cell, it is easy to create or change an automatic culture schedule. is required.

In order to solve these problems, for example, Patent Document 1 presents a program configuration capable of obtaining an automatic culture schedule and its culture history. Further, for example, Patent Document 2 presents means for performing subsequent growth prediction from the cell growth process.

JP 2002-269180 A JP 2001-224366 A

In the culture management program as described in Patent Document 1, although the control method of each element device is shown and a screen for designating it is presented, the culture schedule can be input / selected / changed centrally. Therefore, there are problems that the number of screens to be operated increases and the burden on the operator increases.

In the cell culture prediction system as described in Patent Document 2, it is possible to grasp the state of the cells and then estimate the processing time such as medium replacement by simulation. However, with respect to the estimated processing time such as medium exchange, there is a problem of facilitating information transmission means to the administrator such as a change processing method to the culture schedule and approval of the change.

The present invention has been made in view of such a situation, and allows a worker to easily input information related to a culture schedule, and further includes a cell culture equipped with a graphical user interface that makes it easy to change the culture schedule from cell information. An object is to provide a device, a control device, and a method thereof.

In order to achieve the above object, in the present invention, a cell culturing apparatus, a control mechanism for executing processing of a culture mechanism for culturing cells and culture software for culturing cells in the culture mechanism The control processing unit is separated into a culture schedule software that determines a culture schedule of the culture mechanism unit and a culture control software that controls the culture mechanism unit according to the determined culture schedule when executing the culture software. And a cell culture device configured to be executed.

In order to achieve the above object, in the present invention, a control device for a cell culture device, a control processing unit that executes and processes culture software for culturing cells in the culture mechanism unit, and cell culture And an interface unit capable of displaying the status of the control unit, the control processing unit is configured to display the culture software according to the culture schedule software for determining the culture schedule of the culture mechanism unit and the culture schedule determined by the culture schedule software. A control device configured to be executed separately from control culture control software is provided.

Furthermore, in order to achieve the above object, in the present invention, there is provided a control method for a cell culture device including a control processing unit, and the control processing unit cultivates cells in the culture mechanism unit. There is provided a control method for separately executing a culture schedule software for determining a culture schedule and a culture control software for controlling a culture mechanism unit according to the culture schedule determined by the culture schedule software.

This minimizes the input work for the operator to create a culture schedule, eliminates input errors, facilitates the operation, optimizes the culture schedule based on cell culture predictions, and enables management thereof. Enables stabilization of organizational quality.

It is a figure which shows an example of a function structure of the whole culture | cultivation software of the cell culture apparatus of a 1st Example. It is a figure which shows an example of the whole apparatus structure of the cell culture apparatus based on a 1st Example. It is a figure which shows an example of the main routine of the cell culture software of the cell culture apparatus based on a 1st Example. It is a figure which shows an example of the subroutine of the cell culture software of the cell culture apparatus based on a 1st Example. It is a figure which shows an example of the screen at the time of cell culture software starting based on a 1st Example. It is a figure which shows an example of the main screen of the cell culture control software based on a 1st Example. It is a figure which shows an example of the sub screen of the cell culture control software based on 1st Example. It is a figure which shows an example of the drive system state display of the sub screen of the cell culture control software based on a 1st Example. It is a figure which shows an example of the main screen of the culture schedule software based on a 1st Example. It is a figure which shows an example of the screen of the command list creation software regarding the culture schedule software of a 1st Example. It is a figure which shows an example of the screen of the sequence creation software regarding the culture schedule software based on a 1st Example. It is a figure which shows an example of the screen of the preservation | save data processing software regarding the culture schedule software based on a 1st Example. It is a figure which shows an example of the screen of the microscope position adjustment software regarding the culture schedule software based on 1st Example. It is a figure which shows an example of the screen of the cell growth prediction software regarding the culture schedule software based on 1st Example. It is a figure which shows an example of the system configuration | structure of the cell culture apparatus based on a 1st Example. It is a figure which shows an example of the packet format of the communication protocol of the cell culture apparatus based on a 1st Example. It is a figure which shows an example of the command of the communication protocol of the cell culture apparatus based on a 1st present Example. It is a figure which shows the structural example of the external communication type (remote control type) cell culture apparatus based on a 2nd Example. It is a figure which shows the structural example of the external communication type (remote operation, centralized control type) cell culture apparatus based on a 3rd Example.

Hereinafter, embodiments of the present invention will be described with reference to the accompanying drawings. However, it should be noted that this embodiment is merely an example for realizing the present invention, and does not limit the technical scope of the present invention. In each drawing, the same reference numerals are assigned to common components. In the cell culture device of the present specification, the culture mechanism unit for culturing cells may be referred to as hardware in order to distinguish them from control processing units and control devices that perform control for culturing cells.

The system of the automatic culture apparatus and the Graphical User Interface (GUI) according to the first embodiment are configured to separate the culture schedule software (software) and the automatic culture apparatus control software (software) and communicate necessary information therebetween. Is provided.

Preferred embodiments of the culture schedule software of the present embodiment include command list creation software for creating a culture processing method such as cell seeding and medium exchange, which is called from the main screen of the software for executing the culture schedule in an integrated manner, and these culture processing methods. Sequence creation software to create a timeline, temperature data, etc., stored data processing software to display operation history, microscope positioning software that can focus, time to anticipate cell growth curves Consists of cell growth prediction software that adds an offset to the line.

On the other hand, in the preferred mode of the automatic culture control software of the present embodiment, control of motors and valves, environmental preservation devices, etc., storage of sensor values and operation records, and management of hardware errors of the culture mechanism section are managed. To do. The automatic culture control software normally does not display the main screen but displays a representative sensor value on the sub screen.

In a preferred embodiment of the present embodiment, an error dialog for each of the culture schedule software is displayed when an error on the culture schedule occurs, and an automatic culture control software is displayed when an error on the hardware occurs. Communication is performed between the culture schedule software and the automatic culture control software. For example, when a command for moving the motor is input on the culture schedule software, the command is transmitted to the automatic culture control software by communication, and based on the command. The motor is controlled on the automatic culture control software, and the result information is returned to the culture schedule software. By taking a communication record (log) of this series of operations, it is possible to take a history of the operation of the devices during automatic culture. In addition, when an error occurs on the culture schedule, safe evacuation processing can be executed by the automatic culture control software alone, and safety is improved. In addition, since it is not necessary to consider the input related to automatic culture control, the input work for creating the culture schedule can be minimized, the input error is eliminated from the GUI, the operation is facilitated, and the culture schedule is optimized from the cell culture prediction. Enable and manage.

Hereinafter, an example of the automatic culture apparatus according to the first embodiment will be described in the order of the entire automatic culture software configuration, the culture schedule software configuration, and the automatic culture system configuration.

<Overall configuration of automatic culture software>
The automatic culture apparatus, the overall configuration of the automatic culture software 10, and the role of each software and program will be described with reference to FIGS. 1, 2, 3A, and 3B.

First, the overall configuration of the automatic culture software 10 will be described with reference to FIG. As shown in the figure, the automatic culture software 10 of this embodiment is roughly divided into a culture schedule software 15 and an automatic culture control software 12. The hardware 33 which is a culture mechanism part of the automatic culture apparatus is controlled by the automatic culture control software 12.

As shown in FIG. 2, an automatic culture apparatus 99 according to the present embodiment includes a control processing unit 102 that executes automatic culture software 10 including automatic culture control software 12 and culture schedule software 15, and an operator performs control processing.

Interface units

100 and 101 including at least a display unit and an input unit for instructing the unit 102, and hardware 33 that is a culture mechanism unit of the automatic culture apparatus 99 controlled by the control processing unit 102. The hardware 33 of the automatic culture apparatus depends on the type of the automatic culture apparatus. For example, a motor for driving a manipulator that handles a culture vessel, a pump for supplying a culture medium or a cell solution, and an opening / closing mechanism for a transfer tube Furthermore, although there are refrigerator control units or environmental maintenance facilities such as humidity, it is not limited to these.

As the control processing unit 102 in FIG. 2, for example, a central processing unit (Central Processing Unit: CPU), a memory that is a storage unit, an input unit, a display unit, etc., as will be described later in the system configuration of the automatic culture apparatus 99. An ordinary personal computer (PC) CPU can be used. And the above-mentioned automatic culture software 10 memorized by storage parts, such as memory, is suitably run by CPU of PC. In this specification, the term “control processing unit” means only this CPU, or at least including a storage unit such as a memory for storing various software executed by the CPU. The configuration of the automatic culture apparatus shown in FIG. 2 is referred to as a software built-in type (autonomous type). In the figure, the control processing unit 102 of the automatic culture apparatus 99 executes the automatic culture control software 12 and the culture schedule software 15 of this embodiment, and various hardware is controlled by the control of the automatic culture control software 12. The

As shown in FIG. 1, the automatic culture control software 12 includes an automatic culture control main screen display 13, a sub screen display 14, a command process 22, a device control process 23, a monitoring process 24, a real-time control process 25, a recording process 26, an emergency The function program includes a stop process 27, an error process 28, an option setting process 29, and an opening / startup checklist 30. On the other hand, the culture schedule software 15 includes functional programs for main screen 16 display, command list creation 17, sequence creation 18, saved data processing 19, microscope position adjustment 20, and cell growth prediction 21.

The automatic culture control software 12 and the culture schedule software 15 of the automatic culture software 10 perform communication 31 of necessary information such as commands, command lists, sequences, and the like by the predetermined communication means described with reference to FIGS. 13A and 13B. . The control of the hardware 33 cannot be performed by the culture schedule software 15, and is performed only by communication 32 from the automatic culture control software 12.

FIG. 3A and FIG. 3B show an example of the main routine and subroutine of the automatic culture software 10 of the present embodiment, respectively.
As shown in FIG. 3A, when the automatic culture software is activated, the automatic culture control software 12 is activated (S301). After confirming whether or not all initial items are checked in S302, the automatic culture control software 12, It starts in order of the culture schedule software 15 (S303).
And after confirmation of S304 and S305, an automatic culture | cultivation process (AUTO) is performed (S306). Thereafter, it is periodically checked whether or not the automatic culture process has been completed (S307), and if completed, an end program is executed, an end display is shown on the display unit (S308), and the process ends (S309).

FIG. 3B shows an automatic culture process (AUTO) which is a subroutine of the process flow of FIG. 3A. As is clear from the figure, the AUTO (S310) confirms whether or not the cells are seeded (S311), executes a predetermined sequence (S312 to S314), and determines whether or not a predetermined time has passed in S315. When a predetermined time has elapsed, after executing a plurality of sequences (S316 to S318), in S319, it is confirmed whether all the processes have been completed, and a process of returning to the main routine is performed.

The screen display of the present embodiment when the above automatic culture software 10 is executed will be described with reference to FIGS. Various display screens in the present embodiment are displayed on the display unit of the above-described PC or a display screen that can be observed by other operators. After the start of the automatic culture software 10 in the control processing unit 102, the automatic culture control software 12 starts up. After the processing of the opening / startup checklist 30 from the start screen shown in FIG. The automatic culture control sub-screen 14 in FIG. 5B and the culture schedule main screen 16 in FIG. 6 are displayed on the display unit of the display, and the automatic culture process starts. Each screen display in the above series of flows will be described below.

Referring to FIG. 4, the processing of the opening / startup checklist 30 on the start screen 11 after the start of the automatic culture software 10 by the control processing unit 102 will be described. When the automatic culture software 10 is activated, an activation screen 11 of FIG. 4 is displayed. Here, for example, important predetermined items related to automatic culture processing such as preparation of consumables, etc. in the hardware as a culture mechanism section are described in the checklist 30, and all dialogs 34 are checked. Thus, the start button 35 can be pushed. If any of the items in the checklist 30 does not apply, the cancel button 36 is pressed, and the automatic culture software 10 by the control processing unit 102 is terminated.

Next, referring to FIGS. 5A, 5B, 5C, and 6, the operation of the automatic culture control software 12, the automatic culture control software main screen 13 and the sub screen 14, and the main screen 16 of the culture schedule software 15 are used. Will be described. After pressing the start button 35 on the startup screen 11 in FIG. 4, the sub screen 14 of the automatic culture control software 12 shown in FIG. 5B and the main screen 16 of the culture schedule software 15 shown in FIG. Is displayed.

FIG. 5A shows an automatic culture control main screen 13 of the automatic culture control software 12. This main screen 13 is not normally displayed on the display screen, and is used when detailed setting is necessary or during maintenance. The automatic culture control main screen 13 of FIG. 5A displays the communication status and history between the culture schedule software 15 and the hardware 33, displays sensor values indicating the status from the hardware 33, and controls the details thereof. A button 40 and a control button 41 for controlling the drive system of the hardware 33 are displayed.

From this automatic culture control main screen 13, command process 22, device control process 23, monitoring process 24, real-time control process 25, recording process 26, emergency stop process 27, error process 28 and option setting process 29 of the automatic culture control software 12 It is possible to check all statuses and change their settings.

FIG. 5B shows an automatic culture control sub-screen 14 of the automatic culture control software 12. This sub-screen 14 is normally displayed, and a status display 37 and a drive system state display 38 are displayed. In the automatic culture control sub-screen 14 of FIG. 5B, some functions of the automatic culture control main screen 13 are displayed. Although it can be changed depending on the culture environment, the sensor value display 37 indicating the status related to the culture environment such as the temperature and carbon dioxide concentration, and the hardware 33 related to the automatic culture process, particularly the state 38 of the drive system, are automatically cultured. This is displayed on the screen 14. Although a switching button 42 for switching between the automatic culture control sub-screen 14 and the automatic culture control main screen 13 can be displayed, electronic authentication such as a password can be provided at the time of switching from the viewpoint of security.

FIG. 5C shows a display of culture device error information as an example of the display shown in the drive system status display 38 of the sub-screen 14. As is clear from FIG. 5C, the error name, error details, error occurrence time, and the like are displayed, and the display screen displays the continuation, OK, termination, and cancellation for the operator to select a process corresponding to the error. A button is displayed.

FIG. 6 shows a culture schedule main screen, and automatic culture processing is performed on this main screen 16. A method for performing the automatic culture process will be described below. First, when an automatic culture sequence file created by the sequence creation software 18 to be described later is selected 43, the execution contents are displayed in the command list dialog 44 and the sequence dialog 45, and the culture processing schedule is displayed in the calendar 46. When the contents are checked and the start button 47 is pressed, the automatic culture process starts. At this time, the display of the execution time 48, the next operation time 49, the estimated end time 50, and the calendar 46 is updated when the start button 47 is pressed. In addition, the current status display 51 is changed from being stopped to being automatically cultured. When the automatic culture process is performed, the command being executed and the command list are highlighted in the command list dialog 44 and the sequence dialog 45, respectively.

In addition, the sequence dialog 45 has a timeline display 52, which allows a visual judgment on the execution time of the command list being executed. There is a suspend button 53 and a stop button 54 to stop during the automatic culture process. When the pause button 53 is pressed again, the automatic culture process can be resumed from the paused operation. Since the stop button 54 stops all operations, the automatic culture process cannot be resumed from the same operation. The culture schedule main screen 16 includes software for cell growth prediction 21, microscope position adjustment 20, stored data processing 19, sequence creation 18, and command list creation 17. This has an important role in the operation of the culture schedule main screen 16 for executing the sequence file.
Next, the configuration of each software will be described.

<Composition of culture schedule software>
A command list creation screen and a sequence creation screen as an interface unit for creating a sequence file in this embodiment will be described with reference to FIGS. In the automatic culture process, since the hardware 33 performs cell seeding, medium exchange, cell microscope observation, and the like, each command list is required. Since a command is generally composed of a character string determined by a device designer, it is difficult for an operator to write a command list.

Therefore, the GUI that is an interface unit for facilitating the creation of the command list in this embodiment is the command list creation screen 17 shown in FIG. The command selection dialog 55 has a display such as motor operation, for example. When this is selected, the rotational speed and the rotational speed are input in the command content selection 56 and added to the command list 57, and the command is input after translation. The command list 57 created by such operations can be saved 58 with any name (eg, cell seeding, medium exchange, etc.) as data such as text, and the command list name can be designated and output 59 if necessary. can do. The command list 57 can be corrected by adding 60, deleting 61, and updating 62, and further enabling an operation check 63 for moving the hardware 33.

A GUI for facilitating creation of a sequence for executing the command list 57 created here at a specified time is the sequence creation screen 18 shown in FIG. For example, a medium exchange display is displayed in the command list selection dialog 64, and when this is selected, the time can be input at the command list execution time input 65 and added to the sequence list 66. The sequence list 66 created by such operations can be saved 67 as an arbitrary name (for example, a sequence for corneal cell culture) as data such as text, and the sequence name is designated and output 68 if necessary. be able to. The sequence list 66 has a days specification tab tab 73, and the command list 57 can be input every automatic culture processing day. The sequence list 66 can be modified by adding 69, deleting 70, and updating 71, and further enabling an operation check 72 for moving the hardware 33.

Next, an example of the saved data processing screen 19 for graphing sensor values from the saved data will be described with reference to FIG. In the recording process in the automatic culture control software 12, sensor values relating to the culture environment such as temperature and carbon dioxide concentration are generally stored in a text format. During or after the completion of the automatic culture, the operator searches 74 past culture environment data to check whether the cells are cultured in a normal environment within the automatic culture process.

Therefore, this screen makes it easy for the operator to determine the current or past culture status by graphing the stored data under the necessary conditions. Data to be graphed is selected from the graph display sensor value selection dialog 75. At this time, the maximum and minimum values on the vertical axis of the graph can be determined. When a period to be displayed on the graph is selected in the search dialog 74, the requested graph is displayed on the sensor value graph dialog 76. This graph can be saved in the graph save dialog 77, and past graph data can be outputted in the save data file selection dialog 78. The saved data can be saved in JPEG (Joint Photographic Experts Group), BMP (Bit Map), TIFF (Tagged Image File Format), PNG (Portable Network Graphics), etc. It is also possible to put a sign indicating an error occurrence in the graph displayed in the sensor value graph dialog 76.

An example of the microscope position adjustment screen 20 that enables the position adjustment of the microscope that captures the cell image will be described with reference to FIG. The microscope is moved by inputting a numerical value in the jog dial dialog 79 or a joystick on the screen in the dialog box. In addition, it is possible to move by calling the current position stored in the list or the destination position stored in the past. The current microscope position is displayed on the X, Y, Z value screen 80 as X, Y, Z values. The operation button 81 has ON / OFF such as illumination and camera power supply, and the cell image is displayed on the microscope image 82 by these operations. The cell image displayed on the microscope image 82 can be changed in color tone and sharpness by RGB adjustment 83.

The cell image is focused by changing the Z-axis by the jog dial 79 or by the autofocus 84. For example, when the focus changes in a floating state, an adhesive state, or a layered state, the position of the microscope can be changed by the automatic focus correction offset 84. When a cell image is manually captured, the cell image displayed on the microscope image 82 can be saved in an image format such as JPEG, BMP, TIFF, and PNG by the capture button 85. Storage of cell images by automatic photographing within the culture sequence can be carried out by operation using the command list 44. By displaying this screen 20 during the execution process, the cell image taken from the microscope image 82 can be confirmed in real time.

Referring to FIG. 11, an example of a cell growth prediction screen 21 for changing the schedule for medium exchange and microscopic observation from the cell growth state will be described. When the number of cells obtained from a cell image, a medium component, or the like is plotted on the cell growth graph 86 in the cell growth prediction screen 21, a cell number change 87 until the middle is displayed. Further, the medium replacement date 88 on the culture schedule is displayed as the number of culture days. Therefore, when the cell growth prediction button 90 is pressed, the cell number prediction 91 and the recommended medium replacement date 89 can be predicted from the cell number change 87 so far by a known method. In addition, by configuring the cell growth prediction button 90 so that a known cell number prediction method or parameter processing method can be selected, an optimal prediction method can be selected from the types of cells.

To offset the medium replacement date 88 to the expected medium replacement recommended date 89, the medium replacement date 88 is offset. The setting is made from the offset setting dialog 92 and the sequence 45 is changed by the change button 93. When the changed sequence 45 is canceled and corrected to the initial medium replacement date 88, the cancel button 94 is pressed. The expected end date of culture and the time until the end of culture are displayed 95, and at the end, they are displayed, for example, at the end of culture.

<System configuration of automatic culture equipment>
FIG. 12 is a block diagram showing a configuration of a control system for controlling internal devices in the automatic culture apparatus 99 which is the hardware 33 to be controlled by the automatic culture software 10.

The control system of the automatic culture device 99 includes an interface unit including a display unit 100 that indicates a control state to a user, and an input unit (touch panel, keyboard, mouse, etc.) 101 for inputting data and instructions, and an automatic culture device. A control processing unit 102 configured by a central processing unit (CPU) that controls each operation of 99, a memory 103 for performing operations such as a cache, a communication unit 104 functioning as a network interface, A ROM 105 that stores programs including the automatic culture software 10, parameters, and the like, and a RAM 106 that temporarily stores data and processing results are provided. Note that the communication unit 104 may also be an interface unit.

Furthermore, a medium supply system 109 is provided that includes a heater, carbon dioxide supply, and the like, and an environmental holding device 107, a manipulator 110, a refrigerator control 108 for controlling the environment in the refrigerator, and a pump 111. Among these, the display unit 100 to RAM 106 connected via a bus or a communication path and surrounded by a dotted line correspond to the computer such as the PC described above, and the environment holding device 107 to the pump 111 are automatic culture apparatuses. Corresponds to the hardware 33 as the culture mechanism section.

When the user instructs a culture process to be processed from the input unit 101 or the communication unit 104, the control processing unit 102 performs the real-time control 25 in accordance with a command from the automatic culture software 10 stored in the ROM 105, particularly the automatic culture control software 12. Proceed with temperature 37 ° C, 5% carbon dioxide concentration, humidity 100%, clean environment field. The refrigerator control 108 is performed after the medium supply system 109 is installed. Then, the control processing unit 102 performs cell culture processing in the culture vessel by the manipulator 110 and the pump 111 of the medium supply system 109 according to the program of the automatic culture software 10 stored in the ROM 105. The processing status can be shown to the user at any time by the display unit 100 and the communication unit 104. When the cell culture processing is completed, the display unit 100 and the communication unit 104 indicate the completion to the user, sense that the culture container has been removed or the incubator door has been opened, and the control processing unit 102 has automatic culture software stored in the ROM 105 The termination process is performed according to the termination program of No. 10. As described above, a series of cell culture processes by the automatic culture apparatus 99 can be realized.

As communication 31 which is a transmission path of information such as commands and sequences in the automatic culture apparatus in the present embodiment, a normal LAN (Local Area Network) is used, and UDP (User Datagram Protocol) / existing communication protocol is used. Information can be exchanged using IP (Internet Protocol) or TCP (Transmission Control Protocol) / IP. The communication 32 can be configured similarly.

FIGS. 13A and 13B show an example of a packet format when UDP / IP is used as the communication protocol of the communication 31 in the automatic culture apparatus of the present embodiment.
In the communication 31, commands and responses are realized with the packet format 120 shown in FIG. 13A. In the packet format 120, STX indicates the beginning of the packet, the command indicates the communication content body, ETX indicates the end of the command, and CR indicates the end of the packet.

The table 121 shown in FIG. 13B shows an example of the command and response contents of the communication 31. Corresponding to each item number, a command and a response are set, and an identifier shown in the figure is assigned.

Next, as a second embodiment, an external communication type (remote operation type) automatic culture in which only the automatic culture control software 12 in the automatic culture software 10 of the first embodiment described above is held in the automatic culture apparatus 99. An embodiment of the apparatus will be described. In the following description, only the difference from the first embodiment will be described, but the remaining part can be configured in the same manner as the configuration of the first embodiment. For convenience, the

interface units

100 and 101 are not shown.

14A, in the automatic culture apparatus 99, there are a control processing unit 102 having only the automatic culture control software 12 and hardware 33 connected to the control processing unit 102 via the communication 32, and the culture schedule The software 15 is held inside an external control processing unit 112 connected to a communication 31 that is a communication path to an external network. Then, the automatic culture control software 12 in the control processing unit 102 operates by the control from the culture schedule software 15 operating in the external control processing unit 112 via the communication 31. As a communication protocol in this embodiment, UDP / IP or TCP / IP can also be used. It should be noted that functions such as the opening / startup checklist 30 that are a part of the automatic culture control software 12 in this embodiment can also be transferred to the external control processing unit 112 side. In any case, in the configuration of this embodiment, the control processing unit is a generic name including the control processing unit 102 and the external control processing unit 112.

According to the configuration of the present embodiment, remote operation is possible away from the automatic culture apparatus 99 and the amount of software executed in the control processing unit 102 of the automatic culture apparatus 99 is reduced. It is possible to reduce the burden on the processing unit 99.

Next, with reference to FIG. 14B, an embodiment of an external communication type (remote operation, centralized control type) automatic culture apparatus according to the third embodiment will be described. As in the second embodiment, the following description only describes the differences from the first embodiment and the second embodiment, but the remaining portions can be configured in the same manner as in the first and second embodiments. Similarly, the

interface units

100 and 101 are not shown for convenience.

As shown in FIG. 14B, the configuration of this example has a configuration in which a plurality of automatic culture apparatuses 99 are controlled by an external control processing unit 112 installed remotely. Inside each of the plurality of automatic culture apparatuses 99, similarly to the automatic culture apparatus shown in the second embodiment, the hardware 33 and the control processing unit 102 incorporating the automatic culture control software 12 are installed. The culture control software 12 has a configuration controlled by the corresponding culture schedule software 15 in the external control processing unit 112 via the communication 31. It should be noted that functions such as the opening / startup checklist 30 that are a part of the automatic culture control software 12 in this embodiment can also be transferred to the external control processing unit 112 side. In any case, in the configuration of the present embodiment, the control processing unit is a generic name including the control processing unit 102 and the external control processing unit 112.

According to the configuration of the present embodiment, a plurality of automatic culture apparatuses can be collectively controlled and managed by an operator of the external control processing unit 112 installed remotely.

As described above, in the present invention, the culture schedule software is separated from the automatic culture control software and communicates between the two, and the culture schedule software uses the GUI to input the operator's input work and cells for creating the culture schedule. Minimize the process of changing the schedule from the expected culture and eliminate input errors to facilitate operation. Culture schedule management is performed with the culture schedule software. The automatic culture control software operates in the background and controls the hardware by communicating with the culture schedule software. When the culture schedule software goes down, it is possible to stabilize the quality of the biological tissue to be manufactured by managing it with the automatic culture control software. Furthermore, in the culture schedule software, there are command list creation software for creating the processing method, sequence creation software for creating the processing method for each time, operation history display software, microscope position adjustment software, culture prediction software, The automatic culture control software can control each element device, store sensor values, and manage hardware errors.

In addition, this invention is not limited to the above-mentioned Example, Various modifications are included. The above-described embodiments have been described in detail for easy understanding of the present invention, and are not necessarily limited to those having all the configurations described. In the above embodiment, the automatic culture apparatus has been described as an example. However, in the present invention, it is not necessary that the control of the culture apparatus is entirely automated, and part of the control of cell culture in the cell culture apparatus is a control process. It can also be applied to a cell culture apparatus controlled by some automatic culture control software.

Further, a part of the configuration of one embodiment can be replaced with the configuration of another embodiment, and the configuration of another embodiment can be added to the configuration of one embodiment. Further, it is possible to add, delete, and replace other configurations for a part of the configuration of each embodiment.

In addition, each of the above-described configurations, functions, processing units, processing means, and the like may be realized by hardware by designing a part or all of them with, for example, an integrated circuit. In addition, each configuration, function, and the like have been described by exemplifying a case where they are realized by software by executing a program that realizes each function. However, information on programs, tables, files, and the like that realize each function It can be stored not only in memory but also in recording devices such as hard disks and SSDs (Solid State Drives), or recording media such as IC cards, SD cards, and DVDs, and can be downloaded and installed via a network or the like as necessary. It is also possible to do.

10 Automatic culture software 11 Startup screen 12 Automatic culture control software 13 Main screen 14 Sub screen 15 Culture schedule software 16 Main screen 17 Command list creation (including screen)
18 Sequence creation (including screen)
19 Saved data processing (including screen)
20 Microscope position adjustment (including screen)
21 Cell growth prediction (including screen)
22 Command processing 23 Device control processing 24 Monitoring processing 25 Real-time control processing 26 Recording processing 27 Emergency stop processing 28 Error processing 29 Option setting processing 30 Opening / startup checklist 30
31 Communication 32 Communication 33 Hardware 34 Dialog 35 Start button 36 Cancel button 37 Status display (sub)
38 Drive system status display (sub)
39 Communication Status Display 40 Status Display / Control Button 41 Drive System Control / Control Button 42 Switch Button 43 Sequence File Selection 44 Command List Dialog 45 Sequence Dialog 46 Calendar 47 Start Button 48 Execution Time 49 Next Operation Time 50 End Expected Time 51 Current Status Display 52 Timeline display 53 Pause button 54 Stop button 55 Command selection 56 Command content selection 57 Command list 58 Save 59 Output 60 Add 61 Delete 62 Update 63 Operation check 64 Command list selection 65 Command list execution time input 66 Sequence list 67 Save 68 Output 69 Add 70 Delete 71 Update 72 Operation check 73 Tab 74 Search 75 Graph display sensor value selection 76 Sensor value graph 77 Save rough 78 Saved data file selection 79 Jog dial 80 XYZ value 81 Operation button 82 Microscope image 83 RGB adjustment 84 Auto focus / offset 85 Shooting button 86 Cell growth graph 87 Cell number change 88 Medium replacement date 89 Medium replacement recommended date 90 Cell growth prediction Button 91 Cell number prediction 92 Offset setting 93 Change button 94 Stop button 95 Culture end dialog 99

Automatic culture apparatus

100, 101 Interface unit 102 Control processing unit 103 Memory 104 Communication unit 105 ROM
106 RAM
107 environmental maintenance device 108 refrigerator control 109 medium supply system 110 manipulator 111 pump 112 communication format 113 command list 114 external control processing unit

Claims

A cell culture device,
A culture mechanism for culturing cells;
A control processing unit that executes and executes culture software for culturing cells in the culture mechanism unit,
The control processing unit
When the culture software is executed, the culture schedule software for determining the culture schedule of the culture mechanism unit and the culture control software for controlling the culture mechanism unit according to the determined culture schedule are executed separately.
A cell culture device.
The cell culture device according to claim 1,
The control processing unit transmits the culture schedule determined by the culture schedule software to the culture control software by communication.
A cell culture device.
The cell culture device according to claim 2,
An interface unit;
The control processing unit
Execute the culture software, and display an item checklist for the culture mechanism unit on the interface unit,
A cell culture device.
The cell culture device according to claim 2,
An interface unit;
The control processing unit
Execute the culture control software, and display a screen showing the state of the culture mechanism unit on the interface unit,
A cell culture device.
The cell culture device according to claim 4,
The control processing unit
On the screen displaying the state of the culture mechanism part of the interface part, an error is displayed.
A cell culture device.
The cell culture device according to claim 2,
An interface unit;
The control processing unit
Execute the culture schedule software, and display a screen for creating a sequence of a plurality of commands on the interface unit,
A cell culture device.
The cell culture device according to claim 6,
The culture mechanism unit includes an imaging unit that captures a cell image of the cell,
The control processing unit
Execute the culture schedule software, and based on the captured cell image, adjust the focus of the imaging unit,
A cell culture device.
The cell culture device according to claim 6,
The culture mechanism unit includes at least one type of sensor,
The control processing unit
Execute the culture schedule software, and display the output of the sensor on the interface unit,
A cell culture device.
The cell culture device according to claim 6,
The culture mechanism unit includes an imaging unit that captures a cell image of the cell in culture,
The control processing unit
Execute the culture schedule software, and based on the cell image, predict the growth of the cells in culture, display the growth prediction on the interface unit,
A cell culture device.
The cell culture device according to claim 9,
The control processing unit
Execute the culture schedule software, based on the growth prediction, enabling the change of the sequence,
A cell culture device.
A control device for a cell culture device,
A control processing unit that executes and processes culture software for culturing cells in the culture mechanism unit, and an interface unit that can display the status of the cell culture,
The control processing unit
The culture software is separated into a culture schedule software for determining a culture schedule of the culture mechanism unit and a culture control software for controlling the culture mechanism unit according to the culture schedule determined by the culture schedule software. ,
A control device characterized by that.
The control device according to claim 11,
The control processing unit
A command based on the culture schedule determined by the culture schedule software is transmitted to the culture control software.
A control device characterized by that.
The control device according to claim 12,
The culture mechanism is
An imaging unit that captures an image of the cell;
The control processing unit
The culture schedule software predicts the growth of the cell during culture based on the image of the cell, displays the growth prediction on the interface unit, and can change the culture schedule based on the cell growth prediction And
A control device characterized by that.
A method for controlling a cell culture device comprising a control processing unit,
The control processing unit
In order to culture cells in the culture mechanism,
Culture schedule software for determining a culture schedule of the culture mechanism unit;
In accordance with the culture schedule determined by the culture schedule software, the culture control software for controlling the culture mechanism unit is executed separately.
A control method characterized by that.
The control method according to claim 14, comprising:
The control processing unit
A command based on the culture schedule determined by the culture schedule software is transmitted to the culture control software by communication.
A control method characterized by that.