JP4599937B2 - Automatic culture apparatus and automatic culture system - Google Patents

Description

  The present invention relates to an automatic culture apparatus that automatically cultures cells, and an automatic culture system that remotely controls the automatic culture apparatus via a communication line.

  A culture apparatus for automatically culturing cells is known from Patent Document 1, respectively.

JP 2002-148258 A

  However, in the conventional culture apparatus, when observing the cells, the experimenter had to take out the culture container from the culture apparatus and then individually observe it using a microscope.

The automatic culture system according to claim 1 includes a culture means for storing a culture container and culturing cells, a medium exchange means for exchanging the medium in the culture container with a new medium, observing the state of the cell, and observation means for imaging a magnified image of, media exchange means and observation means and control means for controlling a plurality of automatic culture device connected to a communication line, and, via a communication line, each of the automatic culture A receiving means for receiving an enlarged image of the cell imaged by the observation means provided in the apparatus; an analyzing means for analyzing the culture state of the cell from the received enlarged image of the cell ; a monitor analyzer and transmission means for transmitting the analysis result to the automatic culture device, the control means, based on the analysis result received from the monitor analyzer, characterized that you control the automatic culture device
The automatic culture system according to claim 2 includes a culture means for culturing cells by storing a culture container, a medium exchange means for exchanging the medium in the culture container with a new medium, observing the state of the cells, A plurality of automatic culture apparatuses connected to the communication line, and each of the automatic cultures via the communication line. A receiving means for receiving an enlarged image of a cell imaged by an observation means provided in the apparatus, an analyzing means for analyzing the culture state of the cell from the received enlarged image of the cell, and notification of an analysis result analyzed by the analyzing means A notification generation means for generating a transmission means, a transmission means for transmitting the analysis result analyzed by the analysis means to the automatic culture apparatus from which the enlarged image has been transmitted, and a notification of the analysis result generated by the notification generation means via a communication line. A monitoring analysis device including notification transmission means for transmitting to the user's terminal, and the control means automatically cultures based on the analysis result received from the monitor analysis device when the execution of control is instructed by the user. It characterized that you control the device.
The automatic culture system according to claim 3 includes a culture means for storing a culture container and culturing cells, a medium exchange means for replacing the medium in the culture container with a new medium, observing the state of the cells, A plurality of automatic culture apparatuses connected to a communication line, comprising observation means for taking an enlarged image of the above, a medium exchange means, and a control means for controlling the observation means. Receiving means for receiving enlarged images of the cells imaged by the observation means provided in each automatic culture apparatus via a communication line; and analyzing means for analyzing the culture state of the cells from the received enlarged images of the cells; A monitor analysis apparatus comprising: a notification generation unit that generates a notification of an analysis result analyzed by the analysis unit; and a notification transmission unit that transmits a notification of the analysis result generated by the notification generation unit to a user terminal. When the notification request is received from the user terminal, the enlarged image of the cell is received from the automatic culture apparatus by the receiving means via the communication line, the culture state of the cell is analyzed by the analyzing means, and the notification generating means analysis generates a notification of the results, an automatic culture system according to claim 4, characterized that you send notifications to the terminal of the user by the notification transmission means any of claims 1 to 3 In the automatic culture system according to one item, the automatic culture apparatus is further controlled by a control unit, and further includes passage means for transferring the cells in the culture container to another culture container for passage .
Automatic culture system according to claim 5, in the automatic culture system according to any one of claims 2-4, notification generation means generates the contents of the analysis result of the analysis by the analysis means as a notification of the analysis results It is characterized by doing.
The automatic culture system according to claim 6 is the automatic culture system according to any one of claims 1 to 5, wherein the automatic culture apparatus includes a detection means for detecting a cell culture environment in the culture means, and a detection means. Cell culture environment data transmission means for transmitting the cell culture environment data detected in the step, wherein the reception means receives the cell culture environment data transmitted from the cell culture environment data transmission means. .
The automatic culture system according to claim 7 is the automatic culture system according to claim 6, wherein the detection means detects the pH value and temperature of the medium in the culture container .
The automatic culture system according to claim 8 is the automatic culture system according to claim 6 or 7, wherein the cell culture environment data received by the reception means, the enlarged image of the cell, and the analysis result analyzed by the analysis means are obtained. characterized in that it further have a storage means for storing a time series data associated with individual cells.
The automatic culturing system according to claim 9 is the automatic culturing system according to any one of claims 6 to 8, wherein the monitor analyzer is configured to cultivate the culture means based on the cell culture environment data received by the receiving means. monitors the culture environment of the cells in, it characterized that you detect the failure of the detection means.
Automatic culture system according to claim 10, in the automatic culture system according to any one of claims 1-9, culturing means is characterized Rukoto is controlled by the control means.
The automatic culture system according to claim 11 is the automatic culture system according to any one of claims 1 to 10 , further comprising recording means for recording data used by the analysis means to analyze a cell culture state. The analyzing means comprises analyzing the culture state of the cells using the data recorded in the recording means .
The automatic culture system according to claim 12 is the automatic culture system according to any one of claims 1 to 11 , wherein the analysis result is a cell set by analyzing the culture state of the cell by an analysis unit. wherein the control protocol der Rukoto for culturing.

  According to the present invention, since the state of the cell is automatically observed and the image of the cell is taken, it is not necessary for the experimenter to take out the culture container from the culture apparatus and individually observe it using a microscope. In addition, according to the present invention, the cell image captured by the automatic culture apparatus is analyzed by the monitor analysis apparatus connected via the communication line, and the automatic culture apparatus is controlled based on the analysis result. It is possible to control the automatic culture apparatus from a remote location in consideration of the cell state.

-First embodiment-
FIG. 1 is a block diagram showing a configuration of an embodiment of an automatic culture apparatus according to the first embodiment. FIG. 2 is a diagram schematically showing the automatic culture apparatus shown in FIG. The automatic culture apparatus 100 includes a culture / storage unit 110, a solution exchange unit 120, an observation unit 130, a monitor 140, an input device 150, a control device (PC) 160, and a culture protocol database 170. .

  The culture / storage unit 110 is managed by an environmental control device (not shown) whose internal temperature, humidity, and CO2 concentration are stored, and stores a plurality of culture containers containing cells, such as a petri dish or a well plate, and cultures the cells. . Each culture container in the culture / preservation unit 110 is assigned a serial number so that it can be uniquely identified. In the present embodiment, the culture / storage unit 110 has a constant culture environment, and cells that can be cultured in the same culture environment are cultured in the culture / storage unit 110. The culture / storage unit 110 may be divided into a plurality of sections so that different culture environments can be set for each section.

  The culture / storage unit 110 also includes a PH sensor 110a that detects the PH value of the medium in each culture vessel, and a temperature sensor 110b that detects the temperature in the culture / storage unit 110. The PH sensor 110a and the temperature sensor 110b execute detection at a predetermined time interval, for example, every 10 minutes, and hold the detection result in a memory (not shown) as time-series data of the culture environment. Then, the time-series data of the culture environment is transferred to the control device 160 at predetermined time intervals, for example, every 6 hours. In addition, the culture / storage unit 110 may include a humidity sensor, an osmotic pressure sensor, a gas detection sensor, or the like. These sensors detect the humidity and gas phase composition of the culture / storage unit 110 or the osmotic pressure of the medium. These sensors similarly implement detection at predetermined time intervals and transfer data to the controller 160.

  The solution exchange unit 120 takes out the culture container in which the culture medium needs to be replaced from the culture containers stored in the culture / storage unit 110, and performs the medium exchange, that is, the solution exchange. Further, out of the culture containers stored in the culture / preservation unit 110, the culture container in need of passage is taken out, a part of the cells is taken out, and transferred to another culture container. That is, passaging is performed. The observation unit 130 includes a camera-equipped microscope 130a that captures an observation image of cells. The culture containers stored in the culture / storage unit 110 are sequentially or arbitrarily taken out, and the cells in each culture container are microscopically viewed. An image enlarged at 130a is captured and displayed on the monitor 104. Observation is performed at predetermined time intervals, for example, every 6 hours, and an observation image obtained by observation is transferred to the control device 160. In the present embodiment, an upright microscope is shown as the microscope 130a, but an inverted microscope may be used.

  The monitor 140 displays an image of cells observed by the observation unit 130. The input device 150 is used when the user operates the automatic culture apparatus. The culture protocol database 170 stores the following information for each cell type.

(1) Image processing algorithm The image processing algorithm is an algorithm for performing image processing on an observation image captured by the microscope 130a to determine whether or not there is an abnormality in the cell. The contour of the cell is extracted from the image, the number of cells included in the observation image is calculated, and the degree of cell activity is determined from a comparison with a teaching image input in advance. Based on the number of cells and the activity, it is determined whether or not medium replacement and passage are necessary.
(2) Normal protocol The normal protocol stores information such as a control protocol for automatically culturing cells using the automatic culture apparatus 100, such as medium change every 3 days or passage every 5 days. Has been.

(3) Emergency protocol generation algorithm The emergency protocol generation algorithm is an algorithm for generating an emergency protocol by modifying the normal protocol when abnormalities are detected in cells as a result of analyzing time series data of images and culture environment. It is. For example, when an urgent need for subculture occurs, an emergency protocol generation algorithm is used to modify an ordinary protocol and generate an emergency protocol that is controlled to immediately execute the subculture.
(4) Standard culture environment data The standard culture environment data is environmental data suitable for culturing cells, such as the pH value of the medium in the culture vessel and the temperature in the culture / storage unit 110.

  The control device 160 has an analysis unit 160a configured in software form. Based on the image processing algorithm stored in the culture protocol database 170, the analysis unit 160a analyzes the observation image and the time series data of the culture environment, and determines whether or not there is an abnormality in the cell. Then, based on the presence or absence of abnormality, either the above-described normal protocol or emergency protocol is set as a control protocol. The analysis unit 160a also analyzes not only the observation image but also the time series data of the culture environment.

  In the present embodiment, as described above, the analysis unit 160a calculates the number of cells included in the observation image by extracting the outline of the cell from the observation image by performing image processing based on the image processing algorithm. At the same time, the degree of cell activity is determined from a comparison with a previously input teaching image. Based on the number of cells and the degree of activity, it is determined whether medium replacement and passage are necessary. Then, the control protocol is set based on the determination result. For example, the number of cells present in the microscopic field of the culture container is calculated. As a result, if the number of cells exceeds a predetermined quantity, for example, 1000000 / ml, it is regarded as overgrowth, and it is judged that passage is urgently needed, or the passage after logarithmic amplification is judged and automatic passage is performed. Specifically, from the calculated number of cells, it is determined whether or not medium replacement and passage are necessary based on the following conditions, and a control protocol is set.

(1) If the number of cells is equal to or greater than a preset threshold value, the number of cells in the culture container is excessive, and urgent passage is necessary.
(2) If the number of cells is less than a preset threshold even after a lapse of a predetermined number of days, for example, 3 days from the start date of culture, the number of cells in the culture container has not increased as planned, so the user is warned .
(3) If the pH of the medium suddenly becomes acidic, it is determined that the medium needs to be replaced urgently. Further, if PH tends to be acidic immediately after the medium is changed, it is judged to be confluent and it is judged that passage is urgently required.
(4) If the pH tends to be acidic immediately even though the number of cells is less than the predetermined number, it is regarded as bacterial contamination and a warning is given to the user.
(5) If none of the above (1) to (4) is applicable, neither urgent medium replacement nor passage is required.

  For example, if the result of image processing of the observed image is calculated to contain cells that are equal to or greater than a preset threshold value, this applies to (1) above, so the normal protocol is modified based on the emergency protocol generation algorithm. Generate an emergency protocol to make an emergency passaging. Then, the control device 160 sets the generated emergency protocol as a control protocol, and controls the culture / storage unit 110 and the solution exchange unit 120.

  On the other hand, as a result of image processing of the observation image after the lapse of 3 days from the culture start date, when it is calculated that cells below the preset threshold are included, the above applies to (2). Based on this, the normal protocol is modified to generate an emergency protocol so that the medium is changed in an emergency. Then, the control device 160 sets the generated emergency protocol as a control protocol, and controls the culture / storage unit 110 and the solution exchange unit 120.

  When neither of the above (1) and (2) is applicable, that is, when the above (3) is applicable, the control device 160 sets the normal protocol as the control protocol, and the culture / storage unit 110, And the solution exchange unit 120 is controlled. Note that the analysis unit 160a not only calculates the number of cells, but also calculates the number of cells by dividing a cell region from an image, or pre-teached images, that is, stored images and captured images. The cell activity is calculated by comparison, and the time-series change of the activity is calculated.

  The control device 160 also compares the time series data of the culture environment by the PH sensor 110a and the temperature sensor 110b with the standard culture environment data stored in the culture protocol database 170, so that the cell culture environment is being cultured. Monitor the cells for proper condition. At this time, if there is no detection data from at least one of the PH sensor 110a and the temperature sensor 110b in the time series data of the culture environment, it is determined that the sensor without the data is faulty, A warning is displayed on the monitor 140 to prompt the user to replace parts.

  FIG. 3 is a flowchart showing the operation of the automatic culture apparatus 100 in the first embodiment. Note that the process shown in FIG. 3 shows the flow of the process executed for each culture vessel stored in the culture / storage unit 110, and the process is stored in the culture / storage unit 110. Performed for all culture vessels. In step S10, it is determined whether or not a predetermined time, for example, 6 hours has elapsed since the previous cell observation. If it is determined that a predetermined time has elapsed since the previous cell observation, the process proceeds to step S20. In step S20, the culture / storage unit 110 sequentially takes out the stored culture vessels, observes the cells in each culture vessel with the microscope 130a of the observation unit 130, and then proceeds to step S30.

  In step S30, the analysis unit 160a performs image processing on the observation image of the cells obtained by observation with the microscope 130a, and based on the image processing algorithm stored in the culture protocol database 170, the analysis unit 160a Calculate the number of cells, divide the cell area from the image to calculate the number of cells, compare the pre-teached image with the captured image, calculate the activity of the cell, Calculate time-series changes. Also, the presence / absence of abnormality is determined from the time series data of the culture environment and the time series data of the cell activity. Thereafter, the process proceeds to step S31, and based on the time series data of the culture environment detected by the PH sensor 110a and the temperature sensor 110b, it is monitored whether the current culture environment is maintained in a state suitable for the cells being cultured. The process proceeds to step S40.

  In step S40, it is determined whether or not the cell is abnormal based on the result of the image processing. If it is determined that there is an abnormality in the cell, the process proceeds to step S41, and based on the emergency protocol generation algorithm stored in the culture protocol database 170, the normal protocol is modified to generate an emergency protocol and set as the control protocol . If it is determined that there is no abnormality in the cells, the process proceeds to step S42, and the normal protocol stored in the culture protocol database 170 is set as the control protocol. Then, it progresses to step S50 and performs control with respect to the culture | cultivation / preservation | save part 110 and the solution exchange part 120 based on a control protocol. That is, a culture vessel that needs to be passaged or replaced with a medium is taken out to the solution replacement unit 120, and the passage or the medium is replaced automatically. Thereafter, the process proceeds to step S60.

  In step S60, based on the time series data of the culture environment, it is determined whether or not any sensor has failed. If it is determined that a failure has occurred in any one of the sensors, the process proceeds to step S70, a warning for prompting component replacement is displayed on the monitor 140, and the process ends. When it is determined that no failure has occurred in any of the sensors, the processing is terminated as it is.

As described above, according to the present embodiment, the following operational effects can be obtained.
(1) The cells in the culture container stored in the culture / storage unit 110 are enlarged and imaged by the observation unit 130, and the observation state is image-processed to analyze the culture state of the cells. Based on the analysis result and the analysis result of the time-series data of the culture environment, a control protocol is set, and the cells are automatically cultured by controlling the culture / storage unit 110 and the solution exchange unit 120. As a result, the cells can be automatically cultured without the user's hand, and the labor of the user can be greatly reduced. Furthermore, since no work is performed by the user during subculture or medium exchange, cells can be cultured while maintaining aseptic conditions.

(2) A control protocol is set based on the result of image processing of an observation image obtained by observing cells with the microscope 130a. As a result, a control protocol can be set based on the actual cell state, and passage or medium exchange can be performed at an appropriate timing.

(3) The image processing algorithm, normal protocol, emergency protocol generation algorithm, and standard culture environment data are defined for each cell type and stored in the culture protocol database 170. Thereby, analysis suitable for the characteristics of the cell can be performed. Furthermore, when culturing a new type of cell, it is only necessary to add an image processing algorithm, a normal protocol, an emergency protocol generation algorithm, and standard culture environment data for the new type of cell to the culture protocol database 170. It can be a highly versatile device.

(4) Based on the time series data of the culture environment detected by the PH sensor 110a and the temperature sensor 110b, it is determined whether or not a failure has occurred in any of the sensors, and the failure has occurred in any of the sensors. If it is determined that a warning has been issued, a warning prompting replacement of parts is displayed on the monitor 140. Thereby, the user can detect the failure of the sensor at an early stage.

-Second embodiment-
The automatic culture system in the second embodiment automatically controls the automatic culture apparatus from a remote place via a communication line. FIG. 4 is a block diagram showing a configuration of an embodiment of the automatic culture system according to the second embodiment. The automatic culture system 1 is configured by connecting an automatic culture apparatus 100, a monitor server 300, and a user's PC (terminal) 400 to each other via a communication line 500 such as the Internet, and the analysis server 200 is connected to the monitor server 300. Has been. A plurality of automatic culture apparatuses 100 installed at different bases can be connected to the automatic culture system 1, and each automatic culture apparatus 100 is assigned a device number for uniquely identifying them. In the present embodiment, a case where there is one automatic culture apparatus 100 connected will be described.

  The automatic culture apparatus 100 is configured by removing the analysis unit 160a and the culture protocol database 170 from the automatic culture apparatus 100 according to the first embodiment. The observation image captured by the microscope 130a of the observation unit 130 and the time-series data of the culture environment detected by the PH sensor 110a and the temperature sensor 110b in the culture / storage unit 110 are in a predetermined file format, for example, an XML format. The data is converted and transmitted to the monitor server 300 via the communication line 500 at predetermined time intervals. In addition, the timing at which the time series data of the culture environment detected by the PH sensor 110a and the temperature sensor 110b in the culture / storage unit 110 is transmitted to the monitor server 300, and the observation unit 130 transmits the observation image to the monitor server 300. The timing is set individually for each culture vessel.

  The monitor server 300 includes a culture monitor database 310, an analysis result database 320, and a control device 330. The control device 330 includes a culture state monitoring unit 330a configured in software form, a protocol notification unit 330b, and an analysis result generation notification unit 330c. The culture state monitoring unit 330a receives (monitors) the observation image of the cells from the automatic culture apparatus 100 and the time series data of the culture environment detected by the PH sensor 110a and the temperature sensor 110b via the communication line 500, These data are stored in the culture monitor database 310. When data is received from the automatic culture apparatus 100, an analysis execution instruction is issued to the analysis server 200.

  Similarly to the first embodiment, the time series data of the culture environment detected by the PH sensor 110a and the temperature sensor 110b is compared with the standard culture environment data stored in the culture protocol database 170. Then, it is monitored whether the culture environment in the culture / preservation unit 110 maintains a state suitable for the cells being cultured. If there is no detection data from at least one of the PH sensor 110a and the temperature sensor 110b in the time series data of the culture environment, it is determined that the sensor that does not have the data has failed, and the communication line 500 is connected. The sensor is automatically ordered from the parts manufacturer.

  The protocol notification unit 330b reads a control protocol set by the analysis server 200 described later from the analysis result database 320, and transmits it to the automatic culture apparatus 100 via a communication line. Based on the transmitted control protocol, the automatic culture apparatus 100 controls the culture / storage unit 110 and the solution exchange unit 120 to perform automatic cell culture, as in the first embodiment. The analysis result generation notification unit 330c converts the control protocol stored in the analysis result database 320 into a language that can be understood by a human (user), and then uses the communication protocol via a communication line 500, for example, e-mail. To the PC 400. When the control protocol is converted into a language that can be understood by the user, for example, the petri dish number 1 needs to be changed. As a result, the user can accurately grasp the cell analysis result.

  The analysis server 200 includes a culture protocol database 170 and a control device 220 that are mounted on the automatic culture device 100 in the first embodiment, and the control device 220 is an automatic culture in the first embodiment. It has an analysis unit 160a that is installed in the apparatus 100 and is configured in software form. Accordingly, in the second embodiment, the analysis server 200 performs the analysis process performed by the automatic culture apparatus 100 itself in the first embodiment.

  When the control apparatus 220 detects the analysis execution instruction from the monitor server 300 described above, the control apparatus 220 reads an observation image captured by the automatic culture apparatus 100 from the culture monitor database 310. The analysis unit 160a analyzes the culture state of the cell and sets a control protocol by image processing similar to that of the first embodiment and analysis of time series data of the culture environment. The set control protocol is stored in the analysis result database 320 of the monitor server 300. When the storage in the analysis result database 320 is completed, the monitor server 300 is notified of the completion of analysis.

  5 and 6 are flowcharts showing the operation of the automatic culture apparatus 100 in the second embodiment. FIG. 5 shows a flow of processing in the automatic culture apparatus 100 when transmitting an enlarged image of the captured cell and time series data of the culture environment detected by the PH sensor 110a and the temperature sensor 110b to the monitor server 300. ing. In step S110, it is determined whether or not a predetermined time, for example, 6 hours has elapsed since the previous cell observation. If it is determined that a predetermined time has elapsed since the previous cell observation, the process proceeds to step S120. In step S120, an enlarged image of the cell is captured by the observation unit 130 as in step S20 of FIG.

  Thereafter, the process proceeds to step S121, in which time-series data of the culture environment from a predetermined time before to the present time, that is, time-series data of the culture environment for a predetermined time until the present is read, and the process proceeds to step S130. In step S130, the enlarged image of the cell and the time series data of the culture environment are transmitted to the monitor server 300 via the communication line 500. Thereafter, the process ends.

  FIG. 6 shows a processing flow when the automatic culture apparatus 100 receives a control protocol from the monitor server 300. In step S150, it is determined whether or not the control protocol set as a result of the analysis performed by the analysis server 200 has been received from the monitor server 300. If it is determined that the control protocol has been received, the process proceeds to step S160. In step S160, similar to step S50 in the first embodiment, the culture / storage unit 110 and the solution exchange unit 120 are controlled based on the received control protocol. Thereafter, the process ends.

  Next, processing in the monitor server 300 will be described. FIG. 7 is a flowchart showing the operation of the monitor server 300 in the second mode. In step S210, the culture state monitoring unit 330a receives monitor data from the automatic culture apparatus 100, that is, an observation image of the cells, or time series data of the culture environment detected by the PH sensor 110a and the temperature sensor 110b. to decide. If it is determined that the monitor data has been received, the process proceeds to step S220. In step S220, the received monitor data is stored in culture monitor database 310. Thereafter, the process proceeds to step S230.

  In step S230, an analysis execution instruction is issued to analysis server 200, and the process proceeds to step S240. In step S240, based on the time series data of the culture environment, it is monitored whether the culture environment is in a state suitable for the cells being cultured, and the process proceeds to step S250. In step S250, it is determined whether a failure has occurred in any of the sensors based on the time series data of the culture environment. If it is determined that a failure has occurred in any of the sensors, the process proceeds to step S251, and the sensor that has failed is automatically ordered from the component manufacturer, and the process proceeds to step S260. When it is determined that no failure has occurred in any of the sensors, the process proceeds directly to step S260.

  In step S260, it is determined whether an analysis completion notification has been received from analysis server 200. If it is determined that the analysis completion notification is received from the analysis server 200, the process proceeds to step S270. In step S270, the protocol notification unit 330b reads the control protocol set by the processing in the analysis server 200 described later with reference to FIG. 8 from the analysis result database 320, and transmits it to the automatic culture apparatus 100 via the communication line 500. Thereafter, the process proceeds to step S280, where the analysis result generation notification unit 330c converts the control protocol stored in the analysis result database 320 into words that can be recognized by the user, and then proceeds to step S290.

  In step S290, the data obtained by converting the control protocol into words that can be recognized by the user, the monitoring result as to whether or not the culture environment is suitable for the cells being cultured, and the presence or absence of a sensor failure are communicated. It transmits to PC400 via 500 and notifies a user. Thereafter, the process ends.

  Next, processing in the analysis server 200 will be described. FIG. 8 is a flowchart showing the operation of the analysis server 200 in the second mode. In step S310, it is determined whether an analysis execution instruction from monitor server 300 has been detected. If an analysis execution instruction is detected, the process proceeds to step S320. In step S320, the analysis unit 160a reads the observation image of the cell and the time-series data of the culture environment from the culture monitor database 301 of the monitor server 300, and the image and culture are the same as in step S30 in the first embodiment. The time series data of the environment is analyzed, the cell culture state is analyzed, and the process proceeds to step S330.

  In step S330, as in step S40 of the first embodiment, it is determined whether there is an abnormality in the cell based on the result of the image processing. In the second embodiment, the number of adherent cells, the number of spherical cells, the degree of cell activity, and the like are calculated, and the presence / absence of an abnormality and the degree thereof are calculated. If it is determined that the cell is abnormal, the process proceeds to step S331, and based on the emergency protocol generation algorithm stored in the culture protocol database 170, the normal protocol is modified to generate an emergency protocol as a control protocol.

  If it is determined that there is no abnormality in the cells, the process proceeds to step S332, and the process proceeds to step S340 using the normal protocol stored in the culture protocol database 170 as a control protocol. In step S340, the set control protocol is stored in the analysis result database of the monitor server 300. Thereafter, the process proceeds to step S350, an analysis completion notification is sent to the monitor server 300, and the process ends.

As mentioned above, according to 2nd Embodiment, in addition to the effect in 1st Embodiment, the following effects can be obtained.
(1) The automatic culture apparatus 100 is monitored at a remote place to analyze the cells. As a result, even when the automatic culture apparatus 100 is distributed at a plurality of bases, the automatic culture apparatus 100 can be centrally monitored at one place, and it is necessary to arrange cell culture specialists at various locations. Disappear.
(2) The culture protocol database 170 is arranged on the analysis server 200. As a result, even when data maintenance is required for the culture protocol database 170, it is only necessary to perform the maintenance on the analysis server 200, and the maintenance is easy. In addition, since data is managed in one place, there is no data inconsistency.
(3) The control protocol is converted into words that can be understood by the user and transmitted to the PC 400 of the user. As a result, the user can accurately grasp the cell analysis result.
(4) Based on the time series data of the culture environment detected by the PH sensor 110a and the temperature sensor 110b, it is determined whether or not a failure has occurred in any of the sensors, and the failure has occurred in any of the sensors. If it is determined that the sensor has been used, the sensor is automatically ordered from the component manufacturer via the communication line 500. As a result, it is possible to detect a sensor failure at an early stage and automatically order replacement parts.

-Modification 1-
In the second embodiment described above, the automatic culture apparatus 100 automatically executes control on the culture / storage unit 110 and the solution exchange unit 120 based on the control protocol received from the monitor server 300. However, the present invention is not limited to this and can be modified as follows.

  When the automatic culture apparatus 100 receives a control protocol from the monitor server 300, the automatic culture apparatus 100 does not automatically execute control (automatic culture control) for the culture / storage unit 110 and the solution exchange unit 120, and receives an execution instruction from the user. Wait until. On the other hand, as described above in the second embodiment, the analysis result generation notification unit 330c notifies the user of the analysis result obtained by converting the control protocol into words that can be understood by the user. Whether or not to perform automatic culture control is determined by looking at the notification content.

  When the user determines that automatic culture control is to be performed, the user uses the input device 150 to instruct the start of execution of automatic culture control. The automatic culture apparatus 100 receives an instruction to start execution by the user and executes automatic culture control based on the received control protocol. As a result, when automatic culture control is to be performed, for example, when new cell culture is started, the automatic culture control is not performed in a fully automatic manner. Automatic culture control can be executed after waiting for an instruction from the user.

  Further, the monitor server 300 may transmit only the notification of the analysis result to the PC 400 without transmitting the control protocol to the automatic culture apparatus 100. In this case, the user operates the automatic culture apparatus 100 according to the notification content. Then, work such as passage and medium exchange will be performed.

-Modification 2-
In the second embodiment described above, the automatic culture apparatus 100 automatically observes cells every predetermined time, transmits data to the monitor server 300, and receives the monitor data. An example is shown in which the control protocol set by 200 is transmitted to the automatic culture apparatus 100 and the analysis result is transmitted to the PC 400. However, the present invention is not limited to this, and can be modified as follows.

  That is, when the user wants to know the current cell state, the PC 400 or a mobile phone (not shown) requests the monitor server 300 to notify the analysis result via the communication line 500. When the monitor server 300 detects a notification request for analysis results from the user, the monitor server 300 requests the automatic culture apparatus 100 to transmit monitor data, and presents an observation image of the current cell, the PH sensor 110a, and the temperature sensor 110b. To obtain detection data.

  Thereafter, the analysis result generation notification unit 330c transmits the notification of the analysis result only to the user who has requested it. That is, the protocol notification unit 330b does not transmit a control protocol to the automatic culture apparatus 100. As a result, when the user simply wants to know the current state of the cell, it is possible to receive only the notification of the analysis result without executing the control by the automatic culture apparatus 100.

In addition, it can also deform | transform as follows.
(1) In the first and second embodiments described above, when the time series data of the culture environment detected by the PH sensor 110a and the temperature sensor 110b does not include detection data by any sensor Although an example in which it is determined that the sensor itself has failed has been described, the present invention is not limited to this, and it may be determined that a problem has occurred in the software that controls each sensor. When a software defect is detected, automatic recovery is performed by restarting the software.

(2) In the second embodiment described above, the analysis server 200 includes the analysis unit 106a that performs image processing, analysis processing of time series data of the culture environment, and setting of the control protocol. Although the example which does not perform this process was shown, it is not limited to this, You may deform | transform as follows. For example, after performing image processing of the observation image acquired on the automatic culture apparatus 100, the image processing result is transmitted to the monitor server 300. The analysis server 200 sets a control protocol based on the result of image processing performed by the automatic culture apparatus 100.

(3) In the second embodiment described above, an example in which the monitor server 300 and the analysis server 200 are configured with different hardware has been described. However, the present invention is not limited to this, and the monitor server 300 and the analysis server 200 have, for example. Each function may be implemented on one monitor analysis server.

(4) In the second embodiment described above, as shown in FIG. 5, after an enlarged image of a cell is captured by the automatic culture apparatus 100, the image is immediately transmitted to the monitor server 300, and at the same time, The example in which the time series data of the culture environment for a predetermined time until is transmitted to the monitor server 300 has been described. However, the present invention is not limited to this, and in the automatic culture apparatus 100, an enlarged image of the captured cell is held for a predetermined time set in advance, and when the predetermined time has elapsed since the previous image was transmitted, The enlarged images of the cells that have been stored may be transmitted to the monitor server 300 at once. At this time, the time series data of the culture environment for a predetermined time is transmitted to the monitor server 300 together with the enlarged image of the cells.

(5) In the above-described second embodiment and modification (4), when transmitting data from the automatic culture apparatus 100 to the monitor server 300, an enlarged cell image and time-series data of the culture environment are simultaneously transmitted. However, the enlarged image of the cell and the time-series data of the culture environment may be transmitted to the monitor server 300 at different timings. In this case, in the process in the monitor server 300 shown in FIG. 7, it is determined whether the data received from the automatic culture apparatus 100 is an enlarged image of the cell or time-series data of the culture environment, and based on the determination result. To separate the process.

  That is, when the data received from the automatic culture apparatus 100 is an enlarged image of a cell, an analysis execution instruction is issued to the analysis server 200. On the other hand, if the data received from the automatic culture apparatus 100 is time-series data of the culture environment, any one of the PH sensor 110a and the temperature sensor 110b has failed based on the received time-series data of the culture environment. It is determined whether or not this has occurred.

The correspondence between the constituent elements of the claims and the embodiment will be described. The culture / storage unit 110 corresponds to culture means, the solution exchange unit 120 corresponds to passage means and medium exchange means, and the observation unit 130 corresponds to observation means. The control device 160 corresponds to control means and cell culture environment data transmission means, the analysis unit 160a corresponds to analysis means, and the analysis result database 320 corresponds to storage means. The culture state monitor unit 330a corresponds to a reception unit, the protocol notification unit 330b corresponds to a transmission unit, and the analysis result generation notification unit 330c corresponds to a notification generation unit and a notification transmission unit. The PH sensor 110a and the temperature sensor 110b correspond to detection means, and the analysis server 200 and the monitor server 300 correspond to a monitor analysis device. The culture protocol database 170 corresponds to a recording unit. Note that the present invention is not limited to the configurations in the above-described embodiments as long as the characteristic functions of the present invention are not impaired.

It is a block diagram which shows the structure of one Embodiment of the automatic culture apparatus in 1st Embodiment. It is the figure which represented typically the structure of one Embodiment of the automatic culture apparatus in 1st Embodiment. It is a flowchart figure which shows operation | movement of the automatic culture apparatus 100 in a 1st form. It is a block diagram which shows the structure of one Embodiment of the automatic culture system in 2nd Embodiment. It is a 1st flowchart figure which shows operation | movement of the automatic culture apparatus 100 in a 2nd form. It is a 2nd flowchart figure which shows operation | movement of the automatic culture apparatus 100 in a 2nd form. It is a flowchart figure which shows operation | movement of the monitor server 300 in a 2nd form. It is a flowchart figure which shows the operation | movement of the analysis server 200 in a 2nd form.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Automatic culture system 100 Automatic culture apparatus 110 Culture | cultivation / preservation | save part 110a PH sensor 110b Temperature sensor 120 Solution exchange part 130 Observation part 130a Microscope 140 Monitor 150 Input device 160,220,330 Control apparatus 160a Analysis part 170 Culture protocol database 200 Analysis server 300 monitor server 310 culture monitor database 320 analysis result database 330a culture state monitor unit 330b protocol notification unit 330c analysis result generation notification unit 400 PC
500 communication line

Claims (12)

A culture means for culturing cells by storing a culture vessel;
Medium exchange means for exchanging the medium in the culture vessel with a new medium ;
And observation means for observing the state of the cell, to capture an enlarged image of said cell,
A plurality of automatic culture apparatuses connected to a communication line, the medium exchange means, and a control means for controlling the observation means , and
Receiving means for receiving, via the communication line, an enlarged image of the cells imaged by an observing means provided in each of the automatic culture apparatuses;
From the enlarged image of the received cells, analysis means for analyzing the culture state of the cells;
A monitor analysis device comprising a transmission means for transmitting the analysis result of the analysis means to the automatic culture apparatus via the communication line;
The automatic culturing system, wherein the control means controls the automatic culturing apparatus based on an analysis result received from the monitor analyzing apparatus. A culture means for culturing cells by storing a culture vessel;
Medium exchange means for exchanging the medium in the culture vessel with a new medium;
Observation means for observing the state of the cell and capturing an enlarged image of the cell;
A plurality of automatic culture apparatuses connected to a communication line, the medium exchange means, and a control means for controlling the observation means, and
Receiving means for receiving, via the communication line, an enlarged image of the cells imaged by an observing means provided in each of the automatic culture apparatuses;
From the enlarged image of the received cells, analysis means for analyzing the culture state of the cells;
Notification generation means for generating a notification of the analysis result analyzed by the analysis means;
Transmitting means for transmitting the analysis result analyzed by the analyzing means to the automatic culture apparatus from which the enlarged image is transmitted, via the communication line;
A monitor analysis device comprising a notification transmission means for transmitting a notification of the analysis result generated by the notification generation means to a user terminal;
The said control means controls the said automatic culture apparatus based on the analysis result received from the said monitor analyzer, when execution of control is instruct | indicated by the said user, The automatic culture system characterized by the above-mentioned. A culture means for culturing cells by storing a culture vessel;
Medium exchange means for exchanging the medium in the culture vessel with a new medium;
Observation means for observing the state of the cell and capturing an enlarged image of the cell;
A plurality of automatic culture apparatuses connected to a communication line, the medium exchange means, and a control means for controlling the observation means, and
Receiving means for receiving, via the communication line, an enlarged image of the cells imaged by the observation means provided in each of the automatic culture apparatuses;
An analysis means for analyzing a culture state of the cell from the enlarged image of the received cell;
Notification generation means for generating a notification of the analysis result analyzed by the analysis means;
A monitor analysis device comprising a notification transmission means for transmitting a notification of the analysis result generated by the notification generation means to a user terminal;
When the monitor analyzer receives a notification request from the user terminal, the monitor analyzer receives an enlarged image of the cell from the automatic culture apparatus via the communication line, and the analyzer analyzes the cell. An automatic culture system, wherein the notification generation means generates a notification of the analysis result, and the notification transmission means transmits a notification to the user terminal. In the automatic culture system according to any one of claims 1 to 3,
The automatic culture apparatus is further controlled by the control means, and further comprises passage means for transferring cells in the culture container to another culture container and subcultured. In the automatic culture system as described in any one of Claims 2-4 ,
The notification generation means generates the contents of the analysis result analyzed by the analysis means as a notification of the analysis result. In the automatic culture system according to any one of claims 1 to 5,
The automatic culture apparatus includes:
Detection means for detecting a culture environment of the cells in the culture means;
Cell culture environment data transmission means for transmitting cell culture environment data detected by the detection means,
The automatic culturing system , wherein the receiving unit receives the cell culture environment data transmitted from the cell culture environment data transmitting unit . The automatic culture system according to claim 6,
The automatic culture system , wherein the detection means detects a pH value and a temperature of a medium in a culture vessel . The automatic culture system according to claim 6 or 7,
The cell culture environment data received by the receiving unit, and an enlarged image of the cells, to further have a storage means for storing an analysis result of analyzing the time-series data associated with the individual cells in the analyzer Automatic culture system featuring In the automatic culture system according to any one of claims 6 to 8,
Automatic the monitor analyzer, based on the culture environment data of the cells received by the receiving means, monitors the culture environment of a cell in said culture means, characterized that you detect a failure of the detection means Culture system. In the automatic culture system according to any one of claims 1-9,
The culture unit, an automatic culture system, wherein Rukoto is controlled by said control means. In the automatic culture system according to any one of claims 1 to 10,
The analysis means further comprises a recording means for recording data used for analyzing the culture state of the cells,
The automatic culture system characterized in that the analysis means analyzes the culture state of the cells using data recorded in the recording means . In the automatic culture system according to any one of claims 1 to 11,
The analysis results, an automatic culture system, wherein the cells have been set by analyzing the culture conditions of, characterized by control protocol der Rukoto for culturing cells by the analysis means.

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