A flexible well-mixed milliliter-scale reactor with high oxygen transfer rate for microbial cultivations

作者：Bolic Andrijana^*; Larsson Hilde; Hugelier Siewert; Lantz Anna Eliasson; Kruhne Ulrich; Gernaey Krist V

来源：Chemical Engineering Journal, 2016, 303: 655-666.

DOI：10.1016/j.cej.2016.05.117

• Milliliter-scale bioreactor
• Mixing
• Residence time distribution
• k(L)a
• CFD
• Microbial cultivation

In order to choose the best strain and subsequently develop an optimal bioprocess many experiments need to be performed. Usually this process is expensive and labor intensive with a limited amount of data available. Small-scale bioreactors and high-throughput platforms are becoming an attractive solution and replacement for existing microtiter plates, shaken flasks and bench scale bioreactors.
In this work, a new design of a milliliter-scale bioreactor system is presented and characterized. The entire system consists of a platform with gas connections, heater, temperature sensor and optical fibers on the one side and a bioreactor with special designed magnetic stirrer and non-invasive optical sensors for measurement of pH, dissolved oxygen and optical density on the other side. The system has a high level of flexibility in terms of volume (0.5-2 mL), aeration (sparging and surface aeration) and mixing (one- and bi-directional).
Computational fluid dynamics (CFD) was employed in order to simulate the mixing times, the oxygen transfer rates and the appearance and size of the gas-liquid interfaces in the 1 mL-scale bioreactor with unidirectional mixing and surface aeration.
Mixing performance was tested and the oxygen transfer rate was determined experimentally as well. The obtained results show a good mixing time (between 0.4 s and 2 s) and a high oxygen transfer rate (k(L)a > 1000 h(-1)).
The milliliter-scale bioreactor platform was used to cultivate Saccharomyces cerevisiae and Lactobacillus paracasei.

• 出版日期2016-11-1