JP4731987B2 - Automatic culture equipment - Google Patents

Description

  The present invention relates to an automatic culture apparatus for performing a cell culture test.

In cell culture tests, the current situation is that manual operations such as exchanging the medium in the incubator and reseeding to another incubator for subculture are performed manually. Person is necessary. Then, the automatic culture apparatus which performs a cell culture test automatically is proposed (for example, patent document 1). Since the automatic culture apparatus described in Patent Document 1 is controlled by a programmable CPU according to a culture schedule, the culture schedule can be easily customized.
In general, a cell culture test usually takes a long period of several weeks, during which a plurality of types of drugs are used, including changing the drug in the medium according to the culture schedule. In addition, if the remaining amount of chemicals is insufficient during the culture test, the culture test cannot be continued, and it may be necessary to start over from the beginning. Therefore, it is desirable that the chemical container of the automatic culture apparatus is sufficiently filled with chemicals necessary for the culture schedule. On the other hand, since the chemicals necessary for the culture are expensive, it is desired to fill the chemical container with only the amount required in the culture schedule. Therefore, when the automatic culture test is started, it is necessary to check whether or not the remaining amount of the medicine in the medicine container is filled with an amount necessary for performing the culture schedule.

  By the way, the remaining amount of medicine in the medicine container can be confirmed by subtracting the amount of medicine used in the culture schedule from the initial filling amount in the medicine container, but in the case of the apparatus of Patent Document 1, the peristaltic pump Since the liquid delivery amount is obtained based on the rotation speed, if the obtained liquid delivery amount contains an error, an error occurs in the remaining amount of the medicine in the medicine container.

  On the other hand, in order to accurately detect the amount of liquid to be fed, a method of attaching a device for detecting the amount of chemical to be fed in the middle of the liquid feeding tube is also conceivable (Patent Document 2), but a plurality of measuring devices having different capacities are attached. Since it is necessary, there is a problem that the apparatus becomes complicated.

Japanese Patent Laid-Open No. 2004-016194 JP-A-2004-89095

  As described above, conventionally, when an automatic culture test is started, it is automatically confirmed whether the amount of medicine remaining in the medicine container is filled with an amount necessary for performing the culture schedule. Therefore, there are cases where the remaining amount of chemicals is insufficient during the culture test and the culture test cannot be continued.

  Such a problem is not limited to the start of an automatic culture test, but the culture schedule may be changed during the culture test. Therefore, when the culture schedule is changed, the changed culture schedule is executed. It is necessary to automatically check the remaining amount of chemicals required for this.

  An object of the present invention is to make it possible to automatically determine whether or not the remaining amount of medicine in the medicine container can cover the amount of use necessary for performing the culture schedule.

  The present invention relates to an automatic culture apparatus comprising a medicine supply means for supplying medicine from a medicine container to a cell incubator and a control device for controlling the medicine supply means according to a given culture schedule. A detecting means for detecting the amount of medicine is provided, and the control device obtains a remaining amount of medicine in the medicine container based on a detection signal of the detecting means, and the obtained remaining amount is necessary for performing the culture schedule. It is characterized by comprising a judging means for judging whether or not the chemical use amount can be covered.

  That is, since the amount of medicine in the medicine container is detected and the remaining amount of medicine in the medicine container is obtained based on this, the remaining amount of medicine can be obtained accurately. On the other hand, since the amount of medicine used can be uniquely determined by the culture schedule, whether or not the culture schedule can be achieved can be accurately or appropriately determined by comparing the remaining amount of medicine with the amount of medicine used. As a result, the user can perform a culture test using an automatic culture apparatus with peace of mind.

  In this case, if it is determined that the remaining amount of medicine can cover the amount of medicine used, the execution of the culture schedule is permitted. If it is determined that the remaining amount of medicine cannot cover the amount of medicine used, an alarm is issued. Provide means and notify the user. Thereby, failure of the culture test can be prevented. In addition, it is possible to provide alarm means for issuing an alarm when the remaining amount of medicine reaches a set value or less. Thereby, even if the remaining amount of the medicine is insufficient for some reason during the execution of the culture schedule, it is possible to prompt the user to respond.

  In addition, the control device may be configured to include a medicine supply amount measuring unit that measures a medicine supply amount based on a change in the remaining amount of medicine in the medicine container. Thereby, the chemical supply amount supplied according to the culture schedule can be accurately measured.

  According to the present invention, it is possible to determine whether or not the remaining amount of medicine in the medicine container can cover the amount of use necessary for performing the culture schedule.

  Hereinafter, an embodiment of an automatic culture apparatus to which the present invention is applied will be described with reference to FIGS.

  FIG. 1 is a diagram showing an embodiment of an automatic culture apparatus to which the present invention is applied. As shown in FIG. 1, an automatic culture apparatus 1 according to this embodiment includes an incubator 2 that performs cell culture, an incubator 3 that accommodates the incubator 2, and a chemical container in which chemicals to be supplied to the incubator 2 are stored. And a medicine storage 5 having a plurality (three in the illustrated example) of medicine reserve tanks 4. A liquid supply tube 6 inserted from the top to the bottom is attached to the chemical reserve tank 4, and a pinch valve 7 is provided on the liquid supply tube 6. The liquid feeding tube 6 on the downstream side of the pinch valve 7 is connected to a common liquid feeding tube 8, and the liquid feeding tube 8 is provided so as to be able to inject chemicals into the incubator 1 via a peristaltic pump 9. In addition, an air purge tube 18 is connected to the liquid supply tube 8 at a portion to which the liquid supply tube 6 is commonly connected, and clean purge air is supplied to the air purge tube 18 via a filter 19 and an electromagnetic valve 20. It has come to be. These constitute the chemical supply means of the present embodiment.

  The used chemicals in the incubator 2 are sucked by the ironing pump 11 through the pinch valve 10 and discharged to the waste liquid tank 12. The pinch valve 10 and the ironing pump 11 are controlled by the control CPU 13. A user interface device 14 is connected to the control CPU 13. In addition, a CCD camera 15 is provided for photographing the inside of the incubator 2.

  In the chemical reserve tank 4, unused chemicals are respectively stored and placed on the gantry 21. A weight sensor 17 is attached to the legs of the gantry 21. The weight sensor 17 detects the weight applied to the gantry 21 by detecting the distortion of the legs of the gantry 21 using a known strain sensor or the like.

  Next, the detailed structure of the automatic culture apparatus 1 of this embodiment is demonstrated with an operation | movement. The control CPU 13 controls each part in the automatic culture apparatus 1 according to the culture schedule and cultures the cells in the incubator 2. The incubator 3 is formed such that a culture environment such as a temperature and a CO2 concentration suitable for culturing cells in the incubator 2 can be automatically adjusted.

  The control CPU 13 opens the pinch valve 10 of the chemical reserve tank 4 in which necessary chemicals are stored in accordance with the culture schedule given from the user interface device 14 or the like, for example, in accordance with operations such as medium replacement or passage processing. The squeeze pump 9 is driven to inject a necessary amount of chemical into the incubator 2 through the liquid feeding tube 8. As a result, the cells are cultured in the incubator 2. Further, according to the culture schedule, the pinch valve 10 is opened and the ironing pump 11 is driven to discard used chemicals in the incubator 2. Such an operation is repeated according to the culture schedule, such as changing the chemical in the incubator 2 to the same chemical or changing to a different chemical.

  Here, the structure and operation | movement which concern on the characteristic part of this invention are demonstrated. In general, since the culture schedule must be continuously performed over a long period of several weeks, the culture test cannot be continued if the remaining amount of chemicals is insufficient. Therefore, in this embodiment, before starting the culture schedule, it is automatically confirmed whether or not the necessary amount of medicine is filled in the medicine reserve tank 4. FIG. 2 shows the processing of the control CPU 13 that detects the amount of unused chemical in the chemical reserve tank 4 and determines whether the amount of chemical remaining in the chemical reserve tank 4 can cover the amount of chemical used in the culture schedule. The flowchart of a procedure is shown.

  As shown in FIG. 2, the control CPU 13 receives the instruction for starting the determination operation, and reads the culture schedule set by the user via the user interface device 14 (S1). Then, a total use amount qi for each medicine i used in the read culture schedule is obtained (S2). Next, the output signal of each weight sensor 17 provided in each chemical reserve tank 4 is taken, the weight of the chemical reserve tank 4 is subtracted, the weight of the chemical in the chemical reserve tank 4 is obtained, and based on the specific gravity of the chemical The current remaining amount Qi of each medicine is obtained (S3). Then, the total amount of use qi and the remaining amount of medicine Qi are compared for each medicine, and it is determined whether or not there is enough medicine in each medicine reserve tank 4 when performing the culture schedule (S4). If not enough, a warning is displayed on the screen of the user interface device 14 to prompt the user to respond (S5). If it is sufficient, the culture start button of the user interface device 14 is validated (S6).

  As described above, according to the present embodiment, when the culture schedule is started, the weight of the chemical reserve tank 4 is detected and the remaining amount of the unused chemical is obtained. Therefore, the remaining amount of the chemical can be accurately detected. it can. As a result, it is possible to appropriately determine whether or not the required amount of chemicals can be covered by the culture schedule, so if there is a shortage of chemicals due to some reason, by informing the user that the amount of liquid is insufficient, The failure of the culture test due to lack of chemicals can be prevented.

On the other hand, when the culture start button is operated by the user, the culture control according to the culture schedule is started, and the chemical supply to the incubator 2 is automatically performed by the control CPU 13. FIG. 3 shows a flowchart for controlling the chemical supply amount at this time. The control CPU 13 takes in the detection signal of the weight sensor 17 and detects the chemical remaining amount Qi at the start of liquid feeding (S11). Next, in accordance with the culture schedule, a chemical remaining amount Qe at the end of the liquid supply when the current chemical supply amount is supplied to the incubator 2 is determined (S12). Then, the pinch valve 7 is opened and the ironing pump 9 is driven to start the supply of chemicals to the incubator 2 (S13, S14). Next, while the liquid is being fed, the detection signal of the weight sensor 17 is captured to detect the remaining amount of medicine Qi (S15), and whether or not the remaining amount of medicine Qi has reached the remaining amount of medicine Qe at the end of feeding. Is monitored (S16). When the remaining amount of medicine Qi reaches the remaining amount of medicine Qe, the ironing pump 10 is stopped (S17) and the pinch valve 7 is closed (S18). Thereby, according to this embodiment, since the supply amount of the medicine is measured based on the weight of the medicine reserve tank 4, even if air is mixed into the medicine supply means such as the ironing pump 10, an accurate liquid is obtained. An amount can be supplied to the incubator 2. Although not shown, the control CPU 13 opens the solenoid valve 20 and supplies purge air to the liquid feeding tube 8 and the ironing pump 9 to culture the chemicals remaining in the liquid feeding tube 8 and the ironing pump 9. It is driven out to the container 2 to prevent contamination.
(Example of culture schedule)
Here, with reference to FIG. 4 to FIG. 6, an example of culture control according to a specific culture schedule performed using the automatic culture apparatus of the present embodiment will be described.

  FIG. 4 is a flowchart of the entire culture process according to the culture schedule. As shown in the figure, when a start command for cell culture is input, the control CPU 13 causes the culture to be performed according to the culture schedule (S21). Next, it is determined whether or not the medium replacement scheduled date has been reached (S22). If it is not the medium replacement scheduled date, it is determined whether or not the passage processing scheduled date has been reached (S23). If it is not the scheduled passaging date, the process returns to step S21 and repeats steps S22 and S23.

  If it is determined in step S22 that the scheduled medium replacement date has been reached, a medium replacement process is executed (S26). This medium replacement process will be described later with reference to the flowchart for changing the medium replacement schedule shown in FIG. When the medium exchange process is completed, the process returns to step S21 and the processes of steps S22 and S23 are repeated.

  If it is determined in step S16 that the scheduled passage date has been reached, passage processing is executed (S24). This passaging process will be described later with reference to the flow chart for changing the passaging process schedule shown in FIG. When the passaging process is completed, it is determined whether or not the culture according to the culture schedule is completed in step S25 (S25). When the culture is finished, the cells are collected (S27), and the culture schedule process is finished. When the culture is not finished, the process returns to step S21 to repeat the processes of steps S22 to S25.

  Here, the procedure of the medium exchange process in step S26 will be described with reference to FIG. The control CPU 13 observes the state of the cells based on the image in the incubator 2 taken by the CCD camera 15 (S31), and determines whether or not the number of cells is bad (S32). Whether or not the increase is bad is determined by comparing the number of medium exchange cells in the culture schedule set by the user with the number of cells in the incubator. When the increase is good, the remaining amount of medicine in the medicine reserve tank 4 is detected (S34), and then it is determined whether the remaining amount of medicine is sufficient (S36). The medium is exchanged (S41), the medium exchange process is terminated, and the process returns to the process of FIG. If it is determined in step S36 that the remaining amount of medicine is not sufficient, the process proceeds to step 40, where a medicine remaining amount warning is issued to the user interface device 16 to prompt the user to respond (S40). Return to the process. When the medicine remaining amount warning is issued, the user takes measures such as changing the culture schedule or supplementing the medicine.

  On the other hand, if it is determined in step S32 that the increase is bad, the schedule is extended by one day (S33). Next, the remaining amount of the medicine in the medicine reserve tank 4 is detected (S35), and the amount of medicine used and the amount of remaining medicine are compared with the culture schedule extended for one day, and the possible number of medium exchanges and passages is calculated. (S37). Based on the result, it is determined whether or not the remaining amount of medicine is sufficient (S38). If the remaining amount of medicine is sufficient, the possible number of medium exchanges and passage processes is displayed on the user interface device 16 (S39), the medium exchange process is terminated, and the process returns to the process of FIG. If the remaining amount of medicine is not sufficient, the process proceeds to step 40 to prompt the user to respond, finish the medium replacement process, and return to the process of FIG. The user's correspondence is as described above.

  Next, the processing procedure of the passaging process in step S24 in FIG. 4 will be described with reference to FIG. The control CPU 13 observes the state of the cells based on the image in the incubator 2 photographed by the CCD camera 15 (S51), and determines whether or not the number of cells is bad (S52). Whether or not the increase is bad is determined by comparing the cell density of the culture schedule set by the user with the cell density in the incubator 12 taken. If the number of cells is poor, it is determined whether or not to change to medium exchange (S53). If the number of cells is good, it is determined whether or not to end the culture (S54).

  The determination as to whether or not to change the medium in step S53 is made based on whether or not the cell density in the incubator 12 satisfies the passage density ratio of the culture schedule set by the user. When changing to medium exchange, the schedule is changed to medium exchange (S64), and the process returns to the process of FIG. On the other hand, when not changing to medium replacement, the schedule is extended by one day (S55), the chemical remaining amount detection of the chemical reserve tank 4 is performed (S56), and the medium replacement and passage processing of the schedule changed from the chemical residual amount is performed. The possible number of times is calculated (S58), and it is determined whether the remaining amount of medicine is sufficient (S60). When the remaining amount of the medicine is sufficient, the number of possible medium exchanges and passage processes is displayed on the user interface device 16 (S63), and the process returns to FIG. If the remaining amount of the medicine is not sufficient, a warning of the remaining amount of medicine is given to the user interface device 14 (S64), the user is prompted to respond, the passaging process is terminated, and the process returns to FIG. The user's correspondence is as described above.

  On the other hand, if it is determined in step S52 that the increase in cells is not bad, it is first determined whether or not the culture has ended (S54). This determination is made based on whether or not the cell density of all the cultured cells has reached the cell density at the end of the culture in the culture schedule set by the user. In the case of ending the culture, the process proceeds to step S27 in FIG. 4 to collect cells.

  If the determination in step S54 is not the end of the culture, the remaining amount of medicine in the medicine reserve tank 4 is detected (S57), and it is determined whether the remaining amount of medicine is sufficient (S59). If the remaining amount of medicine is sufficient, the passage process is performed (S62), and the process returns to the process of FIG. If the remaining amount of medicine is not sufficient, a medicine remaining amount warning is issued to the user interface device 16 to prompt the user to respond (S65), the passaging process is terminated, and the process returns to FIG.

  As described in the examples of FIGS. 4 to 6, the initial culture schedule may have to be changed during the culture, and the amount of chemical used changes. Therefore, before the culture schedule is changed, the remaining amount of the medicine in the medicine reserve tank 4 is confirmed to determine whether or not the amount of medicine used in the culture schedule can be covered. In the examples of FIGS. 4 to 6, the culture schedule set at the start of culture is automatically changed in the middle, but the user can arbitrarily change the culture schedule during the culture. In this case as well, it is determined whether or not the remaining amount of chemicals necessary for performing the culture schedule is sufficient, and the culture schedule can be changed to an appropriate culture schedule.

  Moreover, the automatic culture apparatus 1 of the embodiment of the present invention shown in FIG. 1 only shows the configuration necessary for the description of the present invention, and the detectors and the like can be freely customized according to the user's request. it can. For example, instead of the weight sensor 17 for detecting the remaining amount of chemical in the chemical reserve tank 4, a liquid level detection sensor for detecting the liquid level in the chemical reserve tank 4 is provided, and the chemical reserve tank 4 is based on the liquid level. The remaining amount of the medicine may be detected.

It is a line | wire system block diagram of one Embodiment of the automatic culture apparatus formed by applying this invention. It is a flowchart of one Embodiment of the determination processing procedure whether the chemical | medical agent usage which is a characteristic part of this invention is detected and the chemical usage amount used by a culture schedule can be covered. It is a flowchart of an example of the control procedure of a chemical | medical agent supply amount. It is a flowchart which shows an example of the procedure of the culture | cultivation process of the automatic culture apparatus to which this invention is applied. It is a flowchart which shows an example of the culture medium exchange processing procedure containing the change of a culture schedule. It is a flowchart which shows an example of the subculture process procedure containing the change of a culture schedule.

Explanation of symbols

1: Automatic culture device 2: Incubator 3: Incubator 4: Chemical reserve tank 5: Chemical storage 6: Liquid feeding tube 7: Pinch valve 8: Liquid feeding tube 9: Iron pump 10: Pinch valve 11: Iron pump 12: Waste liquid Tank 13: CPU for control
14: User interface device 15: CCD camera 16: Communication pipe 17: Weight sensor

Claims (4)

Detecting the amount of drug in the drug container in an automatic culture apparatus comprising a drug supply means for supplying a drug from a drug container to a cell incubator and a control device for controlling the drug supply means according to a given culture schedule The control device obtains the amount of remaining medicine in the medicine container based on the detection signal of the detecting means, and the amount of medicine used for the obtained amount of remaining medicine to execute the culture schedule. comprising a determining means for determining whether can cover a
An automatic culture apparatus, comprising: alarm means for issuing an alarm when the determination means determines that the remaining amount of the drug cannot cover the amount of the drug used . Detecting the amount of drug in the drug container in an automatic culture apparatus comprising a drug supply means for supplying a drug from a drug container to a cell incubator and a control device for controlling the drug supply means according to a given culture schedule The control device obtains the amount of remaining medicine in the medicine container based on the detection signal of the detecting means, and the amount of medicine used for the obtained amount of remaining medicine to execute the culture schedule. An automatic culture apparatus comprising: a determination unit that determines whether or not the drug can be covered, and an alarm unit that issues an alarm when the remaining amount of the drug in the drug container reaches a set value or less . Said control device, said determining means, when the drug residual amount is judged can cover the amount of chemicals used, to claim 1 or 2, further comprising a permitting means for permitting the execution of the culture schedule The automatic culture apparatus described. The said control apparatus has a chemical | medical agent supply amount measurement means which measures the supply amount of the said chemical | medical agent based on the change of the chemical | medical agent residual amount in the said chemical | medical agent container, The any one of Claim 1 thru | or 3 characterized by the above-mentioned. The automatic culture apparatus described.

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