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

Andrijana Bolic, Hilde Kristina Larsson, Siewert Hugelier, Anna Eliasson Lantz, Ulrich Krühne, Krist Gernaey

Research output: Contribution to journalJournal articleResearchpeer-review


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 (kLa > 1000 h−1).The milliliter-scale bioreactor platform was used to cultivate Saccharomyces cerevisiae and Lactobacillus paracasei.
Original languageEnglish
JournalChemical Engineering Journal
Pages (from-to)655-666
Publication statusPublished - 2016


  • Milliliter-scale bioreactor
  • Mixing
  • Residence time distribution
  • kLa
  • CFD
  • Microbial cultivation

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