Bioprocess Development

 

Bioprocess Development

One of the AVT.BioVT's core competencies is the development of biotechnological processes. The focus is on the use of renewable raw materials, as well as residual or waste streams, e.g. from the food industry or forestry.

Numerous different questions arise concerning the characterization and development of biotechnological processes. For example, the choice of a suitable production organism, the optimisation of the medium composition up to a scale-up from the microplate to the fermenter. Furthermore, the mode of operation such as batch, extended-batch, fed-batch or continuous mode must be determined. Further fields of research are the selection of the optimum temperature and pH value, development of an induction profile, investigation of viscosity behaviour and oxygen demand, or production under defined oxygen limitation (microaerophilic conditions). The AVT.BioVT has a broad expertise in the field of process development of various eukaryotic and prokaryotic microorganisms, plant cell systems, enzyme technology and animal cell culture. Pressurised fermentations (up to 11 bar absolute), as well as synthesis gas fermentations are also among the areas of expertise.

An exemplary process development at the AVT.BioVT starts with obtaining the microbial systems from our university and industrial research partners. Typically, process development starts here on a µL scale in microplates. These offer the advantage of high parallelization and automation with low material and labour costs. In a short time, many relevant parameters such as pH optimum, temperature optimum, sensitivity to osmotic pressure or different media components can be tested. Despite small sample volumes, most important process information can already be obtained on this scale with the help of our in-house developed BioLectors and µRAMOS systems. Moreover, the oxygen consumption of cultivations can be measured online, various (light) induction and temperature profiles can investigated and microaerophilic conditions can be simulated. Even industrially relevant modes of operation, such as batch and fed-batch cultivation, can be examined in small-scale. For example, the precursors of the FeedBeads, now commercially available from Adolf Kühner AG and the FeedPlates were developed at AVT.BioVT1,2. With these technologies, fed-batch cultivations, on e.g. glucose or glycerol, can be performed at the microplate and shake flask scale. In addition, membrane-based fed-batch shake flasks allow a variety of substances, such as carbon sources, ammonium, or pH adjusters, to be added in fed-batch to shake flask cultivations3,4.

Once suitable process conditions have been identified at the µL scale, scale-up usually continues in the shake flask. Using the RAMOS technology for online measurement of the oxygen transfer rates (OTR), carbon dioxide transfer rates (CTR), and respiration quotient (RQ), batch, extended batch, fed-batch, and also continuous processes (COSBIOS) can also be performed here. Online measurement of power input and, more recently, viscosity in shake flasks is also possible.

The last scale-up step is the transfer of the developed processes into the stirred tank fermenter, which is widely used in industrial practice. Numerous 1-2 L laboratory fermenters as well as four pressure fermenters with a reactor volume of 7.5 - 150 L are used. The fermenters are equipped with a variety of online monitoring techniques such as dissolved-gas, pH, heat formation (calorimetry), biomass and off-gas analysis. Process transfer to pilot plant scale in a 150 L pressure fermenter with the option of continuous in-situ permeate separation via a filter module is also possible.

If you have any questions, feel free to contact us via the indicated contact person.

We continuously offer theses on the mentioned topics. You can find student and final theses here access only from the RWTH network). In addition, you are welcome to send us a spontaneous application via our .

Contact

Phone

work
+49 241 80 47873

Email

E-Mail
 
 

References

1 Jeude, M., Dittrich, B., Niederschulte, H., Anderlei, T., Knocke, C., Klee, D. and Büchs, J. (2006), Fed‐batch mode in shake flasks by slow‐release technique. Biotechnol. Bioeng., 95: 433-445. https://doi.org/10.1002/bit.21012

2 Keil, T., Dittrich, B., Lattermann, C. et al. Polymer-based controlled-release fed-batch microtiter plate – diminishing the gap between early process development and production conditions. J Biol Eng 13, 18 (2019). https://doi.org/10.1186/s13036-019-0147-6

3 Bähr, C., Leuchtle, B., Lehmann, C., Becker, J., Jeude, M., Peinemann, F., ... & Büchs, J. (2012). Dialysis shake flask for effective screening in fed-batch mode. Biochemical Engineering Journal, 69, 182-195.

4 Habicher, T, John, A, Scholl, N, et al. Introducing substrate limitations to overcome catabolite repression in a protease producing Bacillus licheniformis strain using membrane‐based fed‐batch shake flasks. Biotechnology and Bioengineering. 2019; 116: 1326– 1340. https://doi.org/10.1002/bit.26948