Environmental Control in Flow Bioreactors

Environmental Control in Flow Bioreactors
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DOI:
10.3390/pr5020016
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发表时间:
2017-06-01
期刊:
影响因子:
3.5
通讯作者:
Ahluwalia, Arti
Ahluwalia, Arti
中科院分区:
工程技术3区
文献类型:
--
作者:
Giusti, Serena;Mazzei, Daniele;Ahluwalia, Arti

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生理学相关的先进体外模型的实现不仅与三维多细胞结构的复制有关,而且与细胞培养环境的维持有关,其中参数,如温度,pH值和静水压力得到精细控制。可调和可重复的培养条件是研究环境敏感细胞的关键,也可用于模拟与温度,压力和pH值的变化相关的病理生理条件。在这里,我们提出了SUITE(体外测试的监督单位)系统,一个平台,能够监测和调整动态细胞培养实验中的局部环境变量。控制系统的物理核心是一个混合室,它可以连接到不同的生物反应器,并作为一个介质储存器配备了pH计和压力传感器。腔室由外部电阻元件加热,温度由热敏电阻控制。专用电子控制单元收集来自传感器的所有数据,并通过调节空气和CO2超压和流量来控制pH值和静水压力。该系统的模块化和施加不同的压力条件的可能性被用来实现门静脉高压模型与内皮细胞和肝细胞。结果表明,SUITE平台能够将细胞培养参数控制和维持在代表生理或病理条件的固定值。因此,它代表了仿生体外模型设计的基本工具,可应用于疾病建模或毒性测试。
The realization of physiologically-relevant advanced in vitro models is not just related to the reproduction of a three-dimensional multicellular architecture, but also to the maintenance of a cell culture environment in which parameters, such as temperature, pH, and hydrostatic pressure are finely controlled. Tunable and reproducible culture conditions are crucial for the study of environment-sensitive cells, and can also be used for mimicking pathophysiological conditions related with alterations of temperature, pressure and pH. Here, we present the SUITE (Supervising Unit for In Vitro Testing) system, a platform able to monitor and adjust local environmental variables in dynamic cell culture experiments. The physical core of the control system is a mixing chamber, which can be connected to different bioreactors and acts as a media reservoir equipped with a pH meter and pressure sensors. The chamber is heated by external resistive elements and the temperature is controlled using a thermistor. A purpose-built electronic control unit gathers all data from the sensors and controls the pH and hydrostatic pressure by regulating air and CO2 overpressure and flux. The system's modularity and the possibility of imposing different pressure conditions were used to implement a model of portal hypertension with both endothelial and hepatic cells. The results show that the SUITE platform is able to control and maintain cell culture parameters at fixed values that represent either physiological or pathological conditions. Thus, it represents a fundamental tool for the design of biomimetic in vitro models, with applications in disease modelling or toxicity testing.