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

Abstract

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 (0.5–2mL), 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 1mL-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 0.4s and 2s) and a high oxygen transfer rate (kLa>1000h−1).The milliliter-scale bioreactor platform was used to cultivate Saccharomyces cerevisiae and Lactobacillus paracasei.