WO2018086563A1 - 双循环控温细胞培养箱及其工作方法 - Google Patents

双循环控温细胞培养箱及其工作方法 Download PDF

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WO2018086563A1
WO2018086563A1 PCT/CN2017/110249 CN2017110249W WO2018086563A1 WO 2018086563 A1 WO2018086563 A1 WO 2018086563A1 CN 2017110249 W CN2017110249 W CN 2017110249W WO 2018086563 A1 WO2018086563 A1 WO 2018086563A1
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tank
cell culture
culture incubator
box body
space
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PCT/CN2017/110249
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French (fr)
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闻路红
胡舜迪
史振志
甘剑勤
施露露
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宁波华仪宁创智能科技有限公司
宁波大学
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Publication of WO2018086563A1 publication Critical patent/WO2018086563A1/zh
Priority to US16/288,017 priority Critical patent/US20190218498A1/en

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS 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
    • C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/12—Means for regulation, monitoring, measurement or control, e.g. flow regulation of temperature
    • C12M41/14—Incubators; Climatic chambers
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS 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
    • C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/12—Means for regulation, monitoring, measurement or control, e.g. flow regulation of temperature
    • C12M41/18—Heat exchange systems, e.g. heat jackets or outer envelopes
    • C12M41/20—Heat exchange systems, e.g. heat jackets or outer envelopes the heat transfer medium being a gas

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  • the invention relates to cell culture, in particular to a double-circulation temperature-controlled cell culture incubator and a working method thereof.
  • the incubator is a special device for simulating the growth and growth of various microorganisms such as cells and viruses in their normal physiological environment. It should have high uniformity of gas concentration, temperature and humidity, good stability, rapid recovery, no condensation, etc. Excellent features.
  • the current incubator forms mainly include:
  • this mode uses the fan to stir the gas in the incubator to flow, which can make the gas local convection significant and the heat exchange is sufficient, but the overall heat exchange will be uneven, and the eddy current and local dead angle will be formed, which will easily lead to bacteria. Breeding
  • Air-sleeve laminar flow which can achieve good temperature uniformity by forming hot gas flow around the incubator, but the heating speed is not fast enough and the heating efficiency is too low.
  • the present invention provides a two-cycle temperature-controlled cell culture incubator with precise temperature control and good temperature uniformity.
  • a double-cycle temperature-controlled cell culture incubator comprising:
  • the second box body is disposed inside the first box body, and a closed space is formed between the second box body and the first box body;
  • a third box body wherein the third box body is disposed in the second box body, and a distance between an upper side portion, a rear side portion, and a bottom side portion of the third box body and an inner wall of the second box body is greater than zero.
  • the formed space communicates with the outside through a gas inlet; the interior of the third case communicates with the formed space through the through holes of the upper side and the bottom side;
  • the first box door is disposed on a front side portion of the first box body, and a sealing member is disposed between the first box body and the first box door;
  • Heating the device being disposed inside the first door, the side of the second case, and the enclosed space;
  • a conveying device for feeding gas in the third tank into the formed space and sending gas at the bottom of the enclosed space to an upper portion
  • the heat insulating device is disposed at an outer side portion of the second case or an inner side portion of the first case.
  • the working method comprises:
  • the heating device and the conveying device are opened, and the gas in the third tank is sent between the upper side of the third tank and the second tank, and is mixed with the gas entering through the gas inlet, along the rear side of the third tank And a space between the second tank flows downwardly between the bottom side of the third tank and the second tank, and finally enters the third tank;
  • the gas between the first tank and the second tank is heated by the heating device, and the conveying device delivers the heated gas, and flows up to the second tank along the space between the rear side of the second tank and the first tank. Between the upper side of the body and the first case, and then flow down the space between the left side portion and/or the right side portion of the second case and the first case to the bottom side of the second case Between the first box and the first box.
  • the present invention has the following beneficial effects:
  • the heating rate is fast. Since the space between the first box body and the second box body is provided with a heating device and a conveying device, the ambient temperature in the third box body is increased, and the heating rate and temperature recovery speed of the cell culture chamber are accelerated;
  • the double-cycle method can accelerate the temperature uniformity of the cell culture chamber in the third tank, thereby improving the temperature control precision; at the same time, the double-cycle heating is mutually insured, thereby avoiding the entire equipment failure caused by the failure of some heating components.
  • FIG. 1 is a schematic cross-sectional view of a two-cycle temperature-controlled cell culture incubator in accordance with an embodiment of the present invention.
  • the cell culture incubator includes:
  • the first case 6 is made of a polished electrolytic stainless steel material
  • box door 4 the box door is disposed on a front side portion of the first box body, and a sealing member is disposed between the first box body and the box door;
  • a second box body 8 the second box body is disposed inside the first box body, and a closed space 10 is formed between the second box body and the first box body;
  • a third case 12 the third case is disposed in the second case, and a distance between an upper side portion, a rear side portion, and a bottom side portion of the third case body and an inner wall of the second case body is greater than zero,
  • the formed space 9 communicates with the outside through the gas inlet 1; the inside of the third case communicates with the space formed by the second case through the through holes of the upper side and the bottom side;
  • the heating device is disposed on an inner side of the box door, an outer portion of the second box body, and a closed space, specifically: six heating sheets 3 and two heaters, respectively disposed inside the box door 4
  • a conveying device 2, 7, 14 for feeding gas in the third tank into the formed space (formed between the third tank and the second tank) and The gas at the inner bottom of the closed space (formed between the second tank and the first tank) is sent to the upper portion;
  • the heat insulating device is disposed on the inner wall of the first box or the outer wall of the second box such that an insulated closed space is formed between the first box and the second box.
  • the heating device and the conveying device are opened, and the gas in the third tank is sent between the upper side of the third tank and the second tank, and is mixed with the gas entering through the gas inlet, along the rear side of the third tank And a space between the second tank flows downwardly between the bottom side of the third tank and the second tank, and finally enters the third tank;
  • the gas between the first tank and the second tank is heated by the heating device, and the conveying device delivers the heated gas, and flows up to the second tank along the space between the rear side of the second tank and the first tank. Between the upper side of the body and the first case, and then flow down the space between the left side portion and/or the right side portion of the second case and the first case to the bottom side of the second case Between the first box and the first box.
  • the conveying device adopts three fans, the first fan 2 is disposed on the upper side of the third box, the second fan 7 is disposed on the upper side of the second box, and the first In the space between the cabinets, the third fan 14 is disposed in the space between the bottom side portion of the second box body and the first box body; there are 8 heating devices, 6 of which are heated sheets, respectively arranged in the box The inside of the door, the upper side of the second box, the bottom side, the right side, the right side and the outer side of the rear side, The outer two heaters and the fan in the enclosed space are combined to form a fan heater; the heat insulating device is provided with an insulating material, and is disposed on the inner wall of the first box; the bottom side of the third box is a perforated plate 13, allowing gas to enter the third tank.
  • the heating device and the conveying device are opened, and under the fan pumping of the upper side of the third tank, the gas in the third tank (ie, the cell culture chamber) flows upward, mixes with the newly entered gas, and then follows the three tanks.
  • the space between the second tank and the second tank flows downwardly, and finally passes through the perforated plate into the third tank, thereby completing gas circulation and improving temperature uniformity;
  • the gas at the bottom of the enclosed space formed by the first tank and the second tank is heated and pumped into the space between the rear side of the second tank and the first tank, and the upward flowing gas enters the second tank.
  • the space between the upper side portion and the first case is again heated and pumped by the fan heater, along the space between the right side of the second case and the first case, between the left side portion and the first case The space flows downwards, completing the circulation of gas in the enclosed space.

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Abstract

提供了一种双循环控温细胞培养箱及其工作方法，包括：第一箱体；第二箱体设置在第一箱体内部，第二箱体和第一箱体之间形成封闭的空间；第三箱体设置在第二箱体内，第三箱体的上侧部、后侧部和底侧部与第二箱体的内壁间的距离大于零；输送器件用于将所述第三箱体内的气体送入所形成的空间内；加热器件设置在箱门的内侧以及第二箱体的侧部；隔热器件设置在所述第一箱体的外侧部或第一箱体的内侧部。

Description

双循环控温细胞培养箱及其工作方法
相关申请的交叉引用
本申请要求于2016年11月10日提交中国专利局的优先权号为2016109881865、名称为“双循环控温细胞培养箱及其工作方法”的中国专利申请的优先权，其全部内容通过引用结合在本申请中。
技术领域
本发明涉及细胞培养，特别涉及双循环控温细胞培养箱及其工作方法。
背景技术
培养箱是模拟各类细胞、病毒等微生物在其正常生理环境下进行培养生长的专用装置，应具有气体浓度、温度和湿度的均匀性高、稳定性好、恢复快速性、无冷凝水现象等优秀特性。为达到这些目的，目前的培养箱形式主要有：
1.箱内紊流，该模式利用风扇搅动培养箱内气体进行流动，能够使气体局部对流显著且热量交换充分，但会导致整体热量交换不均匀，也会形成涡流和局部死角，容易导致细菌滋生；
2.箱内层流，该方式形成箱内层流循环，箱内温度较为均匀，但是箱外温度均匀性较差，且内外温差较大，尤其在暂停工作或关机时，内壁、门与多气路管壁很容易出现冷凝水现象；
3.气套式层流，该方式通过在培养箱周围形成热气流动，能够实现温度均一性好，但是加热速度不够快，加热效率太低。
上述方式都或多或少地影响了细胞培养的等待时间，延长了细胞的培养整个周期，有可能助长细菌的滋生，最终影响细胞的培养成功率与质量。因此，针对现有的加热装置存在的一些不足，亟需开发一种气体浓度、温度和湿度的控制精度高、均一性好、恢复速度快及箱内无冷凝水现象的培养箱加热方式与装置。
发明内容
为解决上述现有技术方案中的不足，本发明提供了一种温控精确、温度均一性好的双循环控温细胞培养箱。
本发明的目的是通过以下技术方案实现的：
一种双循环控温细胞培养箱，所述细胞培养箱包括：
第一箱体；
第二箱体，所述第二箱体设置在所述第一箱体内部，第二箱体和第一箱体之间形成封闭的空间；
第三箱体，所述第三箱体设置在所述第二箱体内，第三箱体的上侧部、后侧部和底侧部与第二箱体的内壁间的距离大于零，所形成的空间通过气体入口与外界连通；所述第三箱体的内部通过上侧部和底侧部的通孔与所述所形成的空间连通；
第一箱门，所述第一箱门设置在所述第一箱体的前侧部上，第一箱体和第一箱门之间具有密封件；
加热器件，所述加热器件设置在所述第一箱门的内侧、第二箱体的侧部和所述封闭的空间内；
输送器件，所述输送器件用于将所述第三箱体内的气体送入所述所形成的空间内以及将所述封闭的空间内底部的气体送到上部；
隔热器件，所述隔热器件设置在所述第二箱体的外侧部或第一箱体的内侧部。
本发明的目的还在于提供了上述细胞培养箱的工作方法，该发明目的通过以下技术方案得以实现：
根据上述的细胞培养箱的工作方法，所述工作方法包括：
加热器件和输送器件开启，第三箱体内的气体被送到第三箱体上侧部和第二箱体之间，和通过气体入口进入的气体混合，沿着第三箱体的后侧部和第二箱体之间的空间向下流动到第三箱体底侧部和第二箱体之间，最后进入所述第三箱体内；
第一箱体和第二箱体之间的气体被加热器件加热，输送器件输送加热后的气体，沿着第二箱体后侧部和第一箱体之间的空间向上流动到第二箱体上侧部和第一箱体之间，之后沿着第二箱体的左侧部和/或右侧部与第一箱体之间的空间向下流动到第二箱体的底侧部和第一箱体之间。
与现有技术相比，本发明具有的有益效果为：
1.升温速度快。由于第一箱体和第二箱体间的空间设有加热器件和输送器件，相当于增加了第三箱体内的环境温度，加快细胞培养室的升温速度及温度恢复速度；
2.温度精确性高、温度均一性好、可靠性高。双循环方式能加快第三箱体内的细胞培养室的温度均匀性，从而提高了温度的控制精度；同时双循环加热互为保险，避免了因部分加热部件失效导致的整个设备失效。
3.无冷凝现象。由于增加了封闭空间内的加热器件和输送器件，使得封闭的空间与第三箱体内培养室维持在相一致的温度，因此有效解决了传感器和各类旁路系统的水蒸气冷凝问题。
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的双循环控温细胞培养箱的剖视简图。
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双循环细胞培养箱的剖视简图，如图1所示，所述细胞培养箱包括：
第一箱体6，如由抛光电解不锈钢材料制成；
箱门4，所述箱门设置在所述第一箱体的前侧部上，第一箱体和箱门之间具有密封件；
第二箱体8，所述第二箱体设置在所述第一箱体内部，第二箱体和第一箱体之间形成封闭的空间10；
第三箱体12，所述第三箱体设置在所述第二箱体内，第三箱体的上侧部、后侧部和底侧部与第二箱体的内壁间的距离大于零，所形成的空间9通过气体入口1与外界连通；所述第三箱体的内部通过上侧部和底侧部的通孔与所述第二箱体所形成的空间连通；
加热器件，所述加热器件设置在所述箱门的内侧、第二箱体的外侧部和封闭的空间内，具体为：6个加热片3和二个加热器，分别设置在箱门4内侧，第二箱体8的上侧部、底侧部、后侧部、右侧部和左侧部；加热器分别设置在第二箱体的上侧部和第一箱体之间、第二箱体的下侧部和第一箱体之间；
输送器件2、7、14，所述输送器件用于将所述第三箱体内的气体送入所述所形成的空间(第三箱体和第二箱体之间形成的)内以及将所述封闭的空间(第二箱体和第一箱体之间形成的)内底部的气体送到上部；
隔热器件，所述隔热器件设置在第一箱体的内壁上或第二箱体的外壁上，使得第一箱体和第二箱体之间形成隔热的封闭空间。
本发明实施例的上述细胞培养箱的工作方法，包括：
加热器件和输送器件开启，第三箱体内的气体被送到第三箱体上侧部和第二箱体之间，和通过气体入口进入的气体混合，沿着第三箱体的后侧部和第二箱体之间的空间向下流动到第三箱体底侧部和第二箱体之间，最后进入所述第三箱体内；
第一箱体和第二箱体之间的气体被加热器件加热，输送器件输送加热后的气体，沿着第二箱体后侧部和第一箱体之间的空间向上流动到第二箱体上侧部和第一箱体之间，之后沿着第二箱体的左侧部和/或右侧部与第一箱体之间的空间向下流动到第二箱体的底侧部和第一箱体之间。
实施例2：
根据本发明实施例1的双循环控温细胞培养箱的应用例。
如图1所示，在该应用例中，输送器件采用三个风扇，第一风扇2设置在第三箱体的上侧部、第二风扇7设置在第二箱体上侧部和第一箱体之间的空间内、第三风扇14设置在第二箱体的底侧部和第一箱体之间的空间内；加热器件有8个，其中6个采用加热片，分别设置在箱门内侧、第二箱体的上侧部、底侧部、右侧部、右侧部和后侧部的外壁上，另 外2个加热器和封闭空间内的风扇组合在一起，形成风扇加热器；隔热器件采用保温材料，设置在所述第一箱体的内壁上；第三箱体的底侧部采用多孔板13，使得气体进入第三箱体内。
该发明实施例的细胞培养箱的工作方法为：
加热器件和输送器件开启，在第三箱体的上侧部的风扇抽送下，第三箱体(即细胞培养室)内的气体向上流动，和新进入的气体混合，之后沿着三箱体和第二箱体之间空间向下流动，最后穿过所述多孔板进入第三箱体内，从而完成气体循环，提高了温度均一性；
第一箱体和第二箱体形成的封闭空间内底部的气体被加热和抽送，进入第二箱体后侧部和第一箱体之间的空间内，向上流动的气体进入第二箱体上侧部和第一箱体之间的空间，再次被风扇加热器加热和抽送，沿着第二箱体右侧部和第一箱体之间、左侧部和第一箱体之间的空间向下流动，从而完成封闭空间内气体的循环。

Claims (15)

  1. 一种双循环控温细胞培养箱，其特征在于：所述细胞培养箱包括：
    第一箱体；
    第二箱体，所述第二箱体设置在所述第一箱体内部，第二箱体和第一箱体之间形成封闭的空间；
    第三箱体，所述第三箱体设置在所述第二箱体内，第三箱体的上侧部、后侧部和底侧部与第二箱体的内壁间的距离大于零，所形成的空间通过气体入口与外界连通；所述第三箱体的内部通过上侧部和底侧部的通孔与所述第二箱体所形成的空间连通；
    箱门，所述箱门设置在所述第一箱体的前侧部上，第一箱体和箱门之间具有密封件；
    加热器件，所述加热器件设置在所述箱门的内侧、第二箱体的侧部和所述封闭的空间内；
    输送器件，所述输送器件被配置成将所述第三箱体内的气体送入所述所形成的空间内以及将所述封闭的空间内底部的气体送到上部；
    隔热器件，所述隔热器件设置在所述第二箱体的外侧部或第一箱体的内侧部。
  2. 根据权利要求1所述的细胞培养箱，其特征在于：所述加热器件设置在所述第二箱体的外壁上。
  3. 根据权利要求1或2所述的细胞培养箱，其特征在于：在所述封闭的空间内，所述加热器件设置在所述第二箱体的上侧部与所述第一箱体的顶部之间，和/或所述加热器件设置在所述第二箱体的下侧部与所述第一箱体的底部之间。
  4. 根据权利要求1-3中任一项所述的细胞培养箱，其特征在于：所述输送器件设置在所述第二箱体的上侧部和所述第一箱体的顶部之间，和/或所述输送器件设置在所述第二箱体的底侧部和所述第一箱体的底部之间。
  5. 根据权利要求1-4中任一项所述的细胞培养箱，其特征在于：所述输送器件设 置在所述第三箱体的上侧部。
  6. 根据权利要求1-5中任一项所述的细胞培养箱，其特征在于：所述输送器件是风扇。
  7. 根据权利要求1-6中任一项所述的细胞培养箱，其特征在于：所述封闭空间内的输送器件和加热器件组合形成风扇加热器。
  8. 根据权利要求1-7中任一项所述的细胞培养箱，其特征在于：所述隔热器件设置在所述第一箱体的内壁上或第二箱体的外壁上。
  9. 根据权利要求1-8中任一项所述的细胞培养箱，其特征在于：所述隔热器件为保温材质的隔热器件。
  10. 根据权利要求1-9中任一项所述的细胞培养箱，其特征在于：所述第三箱体的底侧部采用多孔板。
  11. 根据权利要求1-10中任一项所述的细胞培养箱，其特征在于：所述第二箱体的后侧壁与所述第一箱体的后侧壁之间的剖面形状为文丘里管的剖面形状。
  12. 根据权利要求1-11中任一项所述的细胞培养箱，其特征在于：所述第三箱体的后侧部与所述第二箱体的后侧壁之间的剖面形状为文丘里管的剖面形状。
  13. 根据权利要求1-12中任一项所述的细胞培养箱，其特征在于：所述第三箱体内设有感测所述第三箱体内温度的温度测量仪。
  14. 根据权利要求1-13中任一项所述的细胞培养箱，其特征在于：所述气体入口连接有预热管，外界的气体通过所述预热管经由所述气体入口进入所述所形成的空间。
  15. 根据权利要求1-14任一项所述的细胞培养箱的工作方法，所述工作方法包括：
    加热器件和输送器件开启，第三箱体内的气体被送到第三箱体上侧部和第二箱体之间，和通过气体入口进入的气体混合，沿着第三箱体的后侧部和第二箱体之间的空间向下流动到第三箱体底侧部和第二箱体之间，最后进入所述第三箱体内；
    第一箱体和第二箱体之间的气体被加热器件加热，输送器件输送加热后的气体，沿着第二箱体后侧部和第一箱体之间的空间向上流动到第二箱体上侧部和第一箱体之 间，之后沿着第二箱体的左侧部和/或右侧部与第一箱体之间的空间向下流动到第二箱体的底侧部和第一箱体之间。
PCT/CN2017/110249 2016-11-10 2017-11-09 双循环控温细胞培养箱及其工作方法 WO2018086563A1 (zh)

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