WO2018121728A1 - 细胞培养操作一体化系统及工作方法 - Google Patents

细胞培养操作一体化系统及工作方法 Download PDF

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WO2018121728A1
WO2018121728A1 PCT/CN2017/119795 CN2017119795W WO2018121728A1 WO 2018121728 A1 WO2018121728 A1 WO 2018121728A1 CN 2017119795 W CN2017119795 W CN 2017119795W WO 2018121728 A1 WO2018121728 A1 WO 2018121728A1
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cell culture
gas
regulating device
inner layer
integration system
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French (fr)
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史振志
闻路红
胡舜迪
洪欢欢
甘剑勤
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宁波大学
宁波华仪宁创智能科技有限公司
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Publication of WO2018121728A1 publication Critical patent/WO2018121728A1/zh
Priority to US16/286,552 priority Critical patent/US20190194594A1/en

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    • C12M23/22Transparent or translucent parts
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    • C12M23/24Gas permeable parts
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    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
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    • C12M23/36Means for collection or storage of gas; Gas holders
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    • C12M41/00Means for regulation, monitoring, measurement or control, e.g. flow regulation
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    • C12M41/00Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/12Means for regulation, monitoring, measurement or control, e.g. flow regulation of temperature
    • C12M41/18Heat exchange systems, e.g. heat jackets or outer envelopes
    • C12M41/20Heat exchange systems, e.g. heat jackets or outer envelopes the heat transfer medium being a gas
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    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12M41/00Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/30Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration
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    • C12M41/00Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/48Automatic or computerized control

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  • the invention relates to cell culture, in particular to a cell culture operation integrated system and a working method.
  • Cell culture needs to be in a suitable environment, such as a suitable gas concentration, appropriate cleanliness, suitable temperature and appropriate humidity (usually saturated or high humidity) to ensure safe and normal cell growth.
  • a suitable environment such as a suitable gas concentration, appropriate cleanliness, suitable temperature and appropriate humidity (usually saturated or high humidity) to ensure safe and normal cell growth.
  • cell culture on the market is mainly carried out by cell culture incubators, and cell manipulation is mainly carried out in a clean bench or a biological safety cabinet to prevent contamination.
  • the main disadvantages of this type of cell culture incubator are:
  • the present invention provides an integrated cell culture operation system with low pollution risk, small gas consumption, and high gas concentration control efficiency.
  • a cell culture operation integration system comprising a housing, the front side of the housing having an operating glove;
  • the casing is a double layer structure composed of an inner layer and an outer layer, and the upper wall and the lower wall of the inner layer have through holes; the outer layer has a gas inlet, a gas outlet and a humidification port;
  • the cell culture operation integration system further includes:
  • heating module being disposed in the interlayer
  • the conveying module transports the gas so that the gas circulates in the inner layer and the interlayer.
  • the object of the present invention is also to provide a working method of a cell culture operation integration system with low pollution risk and high control efficiency, and the object of the invention is achieved by the following technical solutions:
  • the working method of the cell culture operation integration system comprises the following steps:
  • the inner wall of the inner layer has no condensed water
  • (A3) Gas enters the inner layer from the through hole of the upper wall of the inner layer.
  • the present invention has the following beneficial effects:
  • the hot air jacket around the inner layer protects the interlayer, and the gas inside the inner layer is heated by air circulation.
  • the temperature in the interlayer is higher than the inner layer, effectively preventing condensation water from appearing on the inner wall of the inner layer and reducing the risk of contamination;
  • FIG. 1 is a schematic structural view of a cell culture operation integration system according to Embodiment 1 of the present invention.
  • FIG. 1 is a schematic structural diagram of a cell culture operation integration system according to an embodiment of the present invention. As shown in FIG. 1, the cell culture operation integration system includes:
  • a housing having a gas inlet, a gas outlet, and a humidification port, and having a two-layer structure composed of an inner layer and an outer layer; the upper and lower walls of the inner layer having through holes; and a front side of the housing having Operating gloves;
  • a conveying module such as a fan, is disposed at a through hole of the upper wall of the inner layer or a lower side of the through hole for conveying the gas in the inner layer to the regulating device so that the gas is in the inner layer Circulating flow in the interlayer;
  • the sheet heater, the heating module is disposed in the interlayer, such as an inner wall of the outer layer, the side interlayer, the upper interlayer, and the lower interlayer have heating modules, wherein the heating module in the front interlayer is Transparent, easy to observe the inner layer, while improving heating uniformity;
  • a filter disposed at a lower portion of the conveying module, the projection of the filter on a horizontal plane coincides with a pattern enclosed by the inner wall of the inner layer on the horizontal surface;
  • a regulating device wherein the regulating device is respectively in a state of storing and releasing a target gas according to different operating parameters, wherein the regulating device is disposed in the upper interlayer; the regulating device is two, which are an oxygen molecular sieve and a carbon dioxide molecular sieve.
  • the pressure molecules are adsorbed and desorbed by pressure swing adsorption technology (PSA) to store and release the target gas;
  • PSA pressure swing adsorption technology
  • a sensor that transmits the measured content of oxygen and carbon dioxide in the inner layer to the processor
  • the processor controls an operating state of the regulating device according to the received content: if the value is lower than the target value, the control device is in a released state by the control; if the control device is in a stored state, if the control device is in a storage state .
  • the working method of the cell culture operation integration system of the embodiment of the invention comprises the following steps:
  • the inner wall of the inner layer has no condensed water
  • the method for controlling the target gas content in the inner layer includes the following steps:
  • the gas sensor detects the content of the target gas such as oxygen and carbon dioxide in the inner layer of the cell culture operation integration system, and transmits the content to the processor;
  • step (B3) If it is necessary to reduce the content of the target gas, proceed to step (B3);
  • step (B4) If it is necessary to raise the content of the target gas, proceed to step (B4);
  • step (B5) If no adjustment is needed, proceed to step (B5);
  • step (B3) controlling the parameters of the regulating device such that the regulating device is in a target gas storage state; under the action of the conveying module, the gas enters the interlayer from the lower wall of the inner layer, and flows upward along the interlayer between the side walls to the upper wall.
  • the target gas in the gas is stored by the regulating device, and finally enters the inner layer from the upper wall of the inner layer; and proceeds to step (B1);
  • step (B4) controlling the parameters of the regulating device, using the regulating device in a target gas release state; under the action of the conveying module, the gas enters the interlayer from the lower wall of the inner layer, and flows upward along the interlayer between the side walls to the upper wall.
  • the target gas stored in the regulating device is released into the gas, and finally enters the inner layer from the upper wall of the inner layer; and proceeds to step (B1);
  • the external gas is injected into the casing through the gas inlet on the casing: if the target gas content in the casing is always low At the target value, the gas with the target gas content higher than the target value is injected, thereby reducing the content of the target gas in the gas in the casing; if the target gas content in the casing is always higher than the target value, the gas having the target gas content lower than the target value is injected. , thereby reducing the content of the target gas in the gas in the casing.
  • the cell culture operation integration system of the embodiment of the present invention is different from Embodiment 1 in that:
  • the regulating device is disposed outside the casing, and the input end and the output end respectively communicate with the interlayer between the sidewalls of the double-layer structure of the casing;
  • a transport module is additionally provided to deliver the gas of the interlayer to the control device.

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Abstract

一种细胞培养操作一体化系统及控制方法,所述细胞培养操作一体化系统包括壳体,所述壳体的前侧具有操作手套;所述壳体为内层、外层构成的双层结构,所述内层的上壁和下壁具有通孔;所述外层具有气体进口、气体出口和加湿口;所述细胞培养操作一体化系统进一步包括:加热模块,所述加热模块设置在所述夹层内;输送模块,所述输送模块输送气体,使得气体在内层、夹层内循环流动,从而具有气体消耗小等优点。

Description

细胞培养操作一体化系统及工作方法 技术领域
本发明涉及细胞培养,特别涉及细胞培养操作一体化系统及工作方法。
背景技术
细胞培养需要在一个合适的环境中,如合适的气体浓度、合适的洁净度、合适的温度及合适的湿度(通常为饱和湿度或高湿度),从而保证细胞安全、正常的生长。
目前,市面上细胞培养主要由细胞培养箱进行,细胞操作主要在洁净工作台或生物安全柜中进行,以防止污染。这类细胞培养箱的主要的不足在于:
1.细胞培养和操作分离,造成传递过程中的污染;
2.细胞操作的洁净工作台或生物安全柜无气体浓度控制和温度控制,无法确保细胞培养环境的一致性,影响细胞的正常生长;
3.高湿环境下,细胞培养箱的内表面出现冷凝水,污染风险大。
发明内容
为解决上述现有技术方案中的不足,本发明提供了一种污染风险小、气体消耗量小、气体浓度控制效率高的细胞培养操作一体化系统。
本发明的目的是通过以下技术方案实现的:
一种细胞培养操作一体化系统,所述细胞培养操作一体化系统包括壳体,所述壳体的前侧具有操作手套;
所述壳体为内层、外层构成的双层结构,所述内层的上壁和下壁具有通孔;所述外层具有气体进口、气体出口和加湿口;
所述细胞培养操作一体化系统进一步包括:
加热模块,所述加热模块设置在所述夹层内;
输送模块,所述输送模块输送气体,使得气体在内层、夹层内循环流动。
本发明的目的还在于提供了一种污染风险小、控制效率高的细胞培养操作一体化系统的工作方法,该发明目的通过以下技术方案得以实现:
细胞培养操作一体化系统的工作方法,所述细胞培养操作一体化系统的工作方法包括以下步骤:
(A1)在输送模块工作下,气体在内层内向下流动;
(A2)通过所述内层下壁的通孔进入夹层的气体在底部夹层、侧部夹层、上部夹层内流动,并被加热模块加热;
所述内层的内壁没有冷凝水;
(A3)气体从所述内层上壁的通孔进入内层内。
与现有技术相比,本发明具有的有益效果为:
1.内层外围的热气套保护夹层,通过空气循环加热内层内部的气体,夹层内的温度要高于内层内部,有效防止内层内壁出现冷凝水,降低了被污染风险;
2.细胞培养操作一体化,有效地增加了细胞的培养量;
3.降低了内层目标气体浓度控制中的气体的损耗,加快了气体浓度控制的效率。
附图说明
参照附图,本发明的公开内容将变得更易理解。本领域技术人员容易理解的是:这些附图仅仅用于举例说明本发明的技术方案,而并非意在对本发明的保护范围构成限制。图中:
图1是根据本发明实施例1的细胞培养操作一体化系统的结构简图。
具体实施方式
图1和以下说明描述了本发明的可选实施方式以教导本领域技术人员如何实施和再现本发明。为了教导本发明技术方案,已简化或省略了一些常规方面。本领域技术人员应该理解源自这些实施方式的变型或替换将在本发明的范围 内。本领域技术人员应该理解下述特征能够以各种方式组合以形成本发明的多个变型。由此,本发明并不局限于下述可选实施方式,而仅由权利要求和它们的等同物限定。
实施例1:
图1示意性地给出了本发明实施例的细胞培养操作一体化系统的结构简图,如图1所示,所述细胞培养操作一体化系统包括:
壳体,所述壳体具有气体入口、气体出口和加湿口,且为内层、外层构成的双层结构;所述内层的上壁和下壁具有通孔;壳体的前侧具有操作手套;
输送模块,如风机,所述输送模块设置在所述内层的上壁的通孔处或通孔的下侧,用于将所述内层内的气体输送到调控装置,使得气体在内层、夹层内循环流动;
加热模块,所述片状加热器,所述加热模块设置在所述夹层内,如外层的内壁,侧部夹层、上部夹层、下部夹层均有加热模块,其中前侧夹层内的加热模块是透明的,便于观察内层,同时提高了加热均匀性;
过滤器,所述过滤器设置在所述输送模块的下部,所述过滤器在水平面上的投影与所述内层的内壁在所述水平面上围成的图形重合;
调控装置,所述调控装置根据工作参数的不同而分别处于目标气体的储存、释放状态,所述调控装置设置在所述上部夹层内;所述调控装置为2个,为氧气分子筛、二氧化碳分子筛,利用变压吸附技术(PSA)对气体分子进行吸附和解吸附,从而储存、释放目标气体;
传感器,所述传感器将测得的内层内的氧气、二氧化碳的含量传送到处理器;
处理器,所述处理器根据接收到的含量控制所述调控装置的工作状态:若低于目标值,通过控制使调控装置处于释放状态;若高于目标值,通过控制使调控装置处于储存状态。
本发明实施例的细胞培养操作一体化系统的工作方法,所述细胞培养操作 一体化系统的工作方法包括以下步骤:
(A1)在输送模块工作下,气体在内层内向下流动;
(A2)通过所述内层下壁的通孔进入夹层的气体在底部夹层、侧部夹层、上部夹层内流动,并被加热模块加热;
所述内层的内壁没有冷凝水;
(A3)气体从所述内层上壁的通孔进入内层内;
内层内目标气体含量的控制方法包括以下步骤:
(B1)气体传感器检测细胞培养操作一体化系统内层内的氧气、二氧化碳等目标气体的含量,并传送到处理器;
(B2)处理器根据接收到的含量去控制调控装置的工作状态:
如需要降低目标气体的含量,进入步骤(B3);
如需要升高目标气体的含量,进入步骤(B4);
如无需调整,进入步骤(B5);
(B3)控制所述调控装置的参数,使调控装置处于目标气体储存状态;在输送模块的作用下,气体从内层的下壁进入夹层内,沿着侧壁间的夹层向上流动到上壁间的夹层内,气体中的目标气体被调控装置储存,最后从内层的上壁进入内层内部;进入步骤(B1);
(B4)控制所述调控装置的参数,使用调控装置处于目标气体释放状态;在输送模块的作用下,气体从内层的下壁进入夹层内,沿着侧壁间的夹层向上流动到上壁间的夹层内,调控装置储存的目标气体释放到气体中,最后从内层的上壁进入内层内部;进入步骤(B1);
(B5)结束;
在上述过程中,如果经过若干次循环,内层内的目标气体含量仍然不能达到目标值,则需通过壳体上的气体入口向所述壳体内注入外来气体:如壳体内目标气体含量始终低于目标值,则注入目标气体含量高于目标值的气体,从而 降低壳体内气体中目标气体的含量;如壳体内目标气体含量始终高于目标值,则注入目标气体含量低于目标值的气体,从而降低壳体内气体中目标气体的含量。
实施例2:
本发明实施例的细胞培养操作一体化系统,与实施例1不同的是:
1.调控装置设置在所述壳体的外部,输入端和输出端分别连通壳体的双层结构的侧壁间的夹层;
2.另设有输送模块,将夹层的气体输送到所述调控装置。

Claims (10)

  1. 一种细胞培养操作一体化系统,所述细胞培养操作一体化系统包括壳体,所述壳体的前侧具有操作手套;其特征在于:
    所述壳体为内层、外层构成的双层结构,所述内层的上壁和下壁具有通孔;所述外层具有气体进口、气体出口和加湿口;
    所述细胞培养操作一体化系统进一步包括:
    加热模块,所述加热模块设置在所述夹层内;
    输送模块,所述输送模块输送气体,使得气体在内层、夹层内循环流动。
  2. 根据权利要求1所述的细胞培养操作一体化系统,其特征在于:所述加热模块为片状加热器件,设置在所述外层的内壁;设置在前侧外层的内壁的加热模块是透明的。
  3. 根据权利要求1所述的细胞培养操作一体化系统,其特征在于:所述加热模块设置在所述外层的上侧、下侧和所有侧部的内壁上。
  4. 根据权利要求1所述的细胞培养操作一体化系统,其特征在于:所述细胞培养操作一体化系统进一步包括:
    过滤器,所述过滤器设置在所述内层上壁的下侧,所述过滤器在水平面上的投影与所述内层的内壁在所述水平面上围成的图形重合。
  5. 根据权利要求1所述的细胞培养操作一体化系统,其特征在于:所述细胞培养操作一体化系统进一步包括:
    调控装置,所述调控装置根据工作参数的不同而分别处于目标气体的储存、释放状态,所述调控装置的输出端连通所述夹层;
    传感器,所述传感器将测得的壳体内的目标气体的含量传送到处理器;
    处理器,所述处理器根据接收到的含量控制所述调控装置的工作状态。
  6. 根据权利要求5所述的细胞培养操作一体化系统,其特征在于:所述调控装置设置在所述夹层内,输送模块设置在所述内层的上壁的通孔的下侧。
  7. 根据权利要求5所述的细胞培养操作一体化系统,其特征在于:所述调控装置设置在所述壳体的外部。
  8. 根据权利要求5所述的细胞培养操作一体化系统,其特征在于:所述目标气体为氧气、二氧化碳,所述调控装置为分子筛。
  9. 根据权利要求1-8任一所述的细胞培养操作一体化系统的工作方法,所述工作方法包括以下步骤:
    (A1)在输送模块工作下,气体在内层内向下流动;
    (A2)通过所述内层下壁的通孔进入夹层的气体在底部夹层、侧部夹层、上部夹层内流动,并被加热模块加热;
    所述内层的内壁没有冷凝水;
    (A3)气体从所述内层上壁的通孔进入内层内。
  10. 根据权利要求9所述的细胞培养操作一体化系统的工作方法,其特征在于:所述工作方法进一步包括以下步骤:
    (B1)气体传感器检测细胞培养操作一体化系统内的目标气体的含量,并传送到处理器;
    (B2)处理器根据接收到的含量去控制调控装置的工作状态:
    如需要降低目标气体的含量,进入步骤(B3);
    如需要升高目标气体的含量,进入步骤(B4);
    如无需调整,进入步骤(B5);
    (B3)控制所述调控装置的参数,使调控装置处于目标气体储存状态;壳体内的流经调控装置时,气体中的目标气体被储存,处理后的气体送回壳体内;进入步骤(B1);
    (B4)控制所述调控装置的参数,使用调控装置处于目标气体释放状态;壳体内的流经调控装置时,目标气体释放到气体中,处理后的气体送回壳体内;进入步骤(B1);
    (B5)结束。
PCT/CN2017/119795 2016-12-31 2017-12-29 细胞培养操作一体化系统及工作方法 WO2018121728A1 (zh)

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