Monitoring state deviations in bioreactors

    公开(公告)号:US11473042B2

    公开(公告)日:2022-10-18

    申请号:US15765208

    申请日:2016-10-28

    IPC分类号: C12M1/34 C12M1/36 G01N27/404

    摘要: The invention relates to a system (100) for monitoring deviations of a state of a cell culture in a bioreactor (104, 106) from a reference state of a cell culture in a reference bioreactor (102). The bioreactor comprises the same medium (M1) as the reference bioreactor. The system comprises: •—a storage medium (114) comprising: •a PACO-reference profile (116) indicative of a deviation of a CO2 off gas rate (ACOR-M-ti) measured in the reference bioreactor from a predicted CO2 off gas rate (ACOR-EXP-ti) of the reference bioreactor; •a data object comprising a medium-specific relation (136) between the pH value of the medium (M1) and a respective fraction of CO2 gas in a gas volume when said medium is in pH-CO2 equilibrium state with said gas volume and lacks the cell culture; •—an interface (128) for receiving (212) a current CO2 off gas rate (ACOBi-M-ti, ACOB2-M-t i) and a current pH value (pHBi-ti) of the medium of the bioreactor (104, 106); •—a comparison unit (130) configured for computing (214, 216): •a PACO value (PACOB1-tir PACOBi-ti) the PACO-value being indicative of a deviation of a CO2 off gas rate (ACOBi-M-ti, ACOB2-M-ti) measured in the bioreactor from a predicted CO2 off gas rate (ACOB1-EXP-ti, ACOB2-E xp-t i). a difference between the computed PACO value (PACOBi-ti, PACOB2-ti) and a respective reference PACO value (PACOR-ti) in the PACO-reference profile (116).

    IDENTIFICATION OF CALIBRATION DEVIATIONS OF pH-MEASURING DEVICES

    公开(公告)号:US20220325223A1

    公开(公告)日:2022-10-13

    申请号:US17575008

    申请日:2022-01-13

    摘要: The invention relates to a comparison unit (130) configured for determining if a first pH measuring device of a first tank (104; 106) is affected by a pH-measuring problem, the comparison unit being configured for: receiving a first CO2 concentration and a first pH value, the first CO2 concentration being a CO2 concentration of a first gas volume above a medium in a first tank, the first CO2 concentration and the first pH value being measured at a first time when the medium in the first tank is in pH-CO2 equilibrium state with the first gas volume and before said equilibrium state is modified by the metabolism of a cell culture in the first tank, the first pH value being a measured value provided by a first pH measuring device operatively coupled to the first tank (102); receiving a second CO2 concentration and a second pH value, the second CO2 concentration being a CO2 concentration of a second gas volume above a medium in a second tank, the second CO2 concentration and the second pH value being measured at a second time when the medium in the second tank is in pH-CO2 equilibrium state with the second gas volume and before said equilibrium state is modified by the metabolism of a cell culture, the second pH value being a measured value provided by a second pH measuring device; comparing the first and second pH values and CO2 concentrations for determining if comparing (206), by the comparison unit, the first and second pH values and comparing the first and second CO2 concentrations for determining if the first pH measuring device is affected by the pH-measuring problem.

    Identification of calibration deviations of pH-measuring devices

    公开(公告)号:US11371006B2

    公开(公告)日:2022-06-28

    申请号:US15765222

    申请日:2016-10-28

    摘要: The invention relates to a comparison unit (130) configured for determining if a first pH measuring device of a first tank (104; 106) is affected by a pH-measuring problem, the comparison unit being configured for: —receiving a first CO2 concentration and a first pH value, the first CO2 concentration being a CO2 concentration of a first gas volume above a medium in a first tank, the first CO2 concentration and the first pH value being measured at a first time when the medium in the first tank is in pH-CO2 equilibrium state with the first gas volume and before said equilibrium state is modified by the metabolism of a cell culture in the first tank, the first pH value being a measured value provided by a first pH measuring device operatively coupled to the first tank (102); —receiving a second CO2 concentration and a second pH value, the second CO2 concentration being a CO2 concentration of a second gas volume above a medium in a second tank, the second CO2 concentration and the second pH value being measured at a second time when the medium in the second tank is in pH-CO2 equilibrium state with the second gas volume and before said equilibrium state is modified by the metabolism of a cell culture, the second pH value being a measured value provided by a second pH measuring device; —comparing the first and second pH values and CO2 concentrations for determining if comparing (206), by the comparison unit, the first and second pH values and comparing the first and second CO2 concentrations for determining if the first pH measuring device is affected by the pH-measuring problem.

    Monitoring state deviations in bioreactors
    5.
    发明申请

    公开(公告)号:US20180273885A1

    公开(公告)日:2018-09-27

    申请号:US15765208

    申请日:2016-10-28

    IPC分类号: C12M1/34 G01N27/404 C12M1/36

    摘要: The invention relates to a system (100) for monitoring deviations of a state of a cell culture in a bioreactor (104, 106) from a reference state of a cell culture in a reference bioreactor (102). The bioreactor comprises the same medium (M1) as the reference bioreactor. The system comprises: •—a storage medium (114) comprising: •a PACO-reference profile (116) indicative of a deviation of a C02 off gas rate (ACOR-M-ti) measured in the reference bioreactor from a predicted C02 off gas rate (ACOR-EXP-ti) of the reference bioreactor; •a data object comprising a medium-specific relation (136) between the pH value of the medium (M1) and a respective fraction of C02 gas in a gas volume when said medium is in pH-C02 equilibrium state with said gas volume and lacks the cell culture; •—an interface (128) for receiving (212) a current C02 off gas rate (ACOBi-M-ti, ACOB2-M-t i) and a current pH value (pHBi-ti) of the medium of the bioreactor (104, 106); •—a comparison unit (130) configured for computing (214, 216): •a PACO value (PACOB1-tir PACOBi-ti) the PACO-value being indicative of a deviation of a C02 off gas rate (ACOBi-M-ti, ACOB2-M-ti) measured in the bioreactor from a predicted C02 off gas rate (ACOB1-EXP-ti, ACOB2-E xp-t i). a difference between the computed PACO value (PACOBi-ti, PACOB2-ti) and a respective reference PACO value (PACOR-ti) in the PACO-reference profile (116).

    Identification of calibration deviations of pH-measuring devices

    公开(公告)号:US11866686B2

    公开(公告)日:2024-01-09

    申请号:US17575008

    申请日:2022-01-13

    摘要: The invention relates to a comparison unit (130) configured for determining if a first pH measuring device of a first tank (104; 106) is affected by a pH-measuring problem, the comparison unit being configured for:



    receiving a first CO2 concentration and a first pH value, the first CO2 concentration being a CO2 concentration of a first gas volume above a medium in a first tank, the first CO2 concentration and the first pH value being measured at a first time when the medium in the first tank is in pH-CO2 equilibrium state with the first gas volume and before said equilibrium state is modified by the metabolism of a cell culture in the first tank, the first pH value being a measured value provided by a first pH measuring device operatively coupled to the first tank (102);
    receiving a second CO2 concentration and a second pH value, the second CO2 concentration being a CO2 concentration of a second gas volume above a medium in a second tank, the second CO2 concentration and the second pH value being measured at a second time when the medium in the second tank is in pH-CO2 equilibrium state with the second gas volume and before said equilibrium state is modified by the metabolism of a cell culture, the second pH value being a measured value provided by a second pH measuring device;
    comparing the first and second pH values and CO2 concentrations for determining if comparing (206), by the comparison unit, the first and second pH values and comparing the first and second CO2 concentrations for determining if the first pH measuring device is affected by the pH-measuring problem.

    Identification of calibration deviations of pH-measuring devices

    公开(公告)号:US20180216059A1

    公开(公告)日:2018-08-02

    申请号:US15765222

    申请日:2016-10-28

    摘要: The invention relates to a comparison unit (130) configured for determining if a first pH measuring device of a first tank (104; 106) is affected by a pH-measuring problem, the comparison unit being configured for: —receiving a first CO2 concentration and a first pH value, the first CO2 concentration being a CO2 concentration of a first gas volume above a medium in a first tank, the first CO2 concentration and the first pH value being measured at a first time when the medium in the first tank is in pH-CO2 equilibrium state with the first gas volume and before said equilibrium state is modified by the metabolism of a cell culture in the first tank, the first pH value being a measured value provided by a first pH measuring device operatively coupled to the first tank (102); —receiving a second CO2 concentration and a second pH value, the second CO2 concentration being a CO2 concentration of a second gas volume above a medium in a second tank, the second CO2 concentration and the second pH value being measured at a second time when the medium in the second tank is in pH-CO2 equilibrium state with the second gas volume and before said equilibrium state is modified by the metabolism of a cell culture, the second pH value being a measured value provided by a second pH measuring device; —comparing the first and second pH values and CO2 concentrations for determining if comparing (206), by the comparison unit, the first and second pH values and comparing the first and second CO2 concentrations for determining if the first pH measuring device is affected by the pH-measuring problem.

    FEED MIXING DEVICE AND ITS USE
    8.
    发明申请
    FEED MIXING DEVICE AND ITS USE 审中-公开
    进料混合装置及其使用

    公开(公告)号:US20140051121A1

    公开(公告)日:2014-02-20

    申请号:US13909591

    申请日:2013-06-04

    IPC分类号: C12M1/00 C12P21/00

    摘要: Herein is reported a feed mixing device for adding feed solutions with a non-physiologically pH value to a cell cultivation vessel comprising a chamber for mixing the feed solutions prior to their addition to the cell cultivation vessel as well as its use. With the feed mixing device as reported herein feed components can be provided in solution at a pH value at which they have good solubility and/or good stability whereby the pH value can be clearly different from the pH value of the cultivation medium, i.e. different from the physiological pH value. This allows performing the cultivation with more flexibility compared to a cultivation in which the pH value of the feed solution is limited to a small range around the pH value of the cultivation.

    摘要翻译: 本文报道了一种用于将细胞培养容器中添加具有非生理学pH值的进料溶液加入到细胞培养容器中的饲料混合装置,所述培养容器包括用于将饲料溶液加入细胞培养容器之前混合饲料溶液的室以及其用途。 使用本文所述的进料混合装置,可以在溶液中以pH值提供给料组分,在该pH下它们具有良好的溶解性和/或良好的稳定性,因此pH值可以与培养基的pH值明显不同,即不同于 生理pH值。 与将培养液的pH值限制在培养pH值附近的小范围的培养相比,可以更有效地进行培养。