![]() ![]() ![]() A major advantage of 3D-printed microsystems over traditional manufacturing methods is that desired prototypes can be produced within just a few hours of the completion of design, in high-resolution structures in the range of a few micrometers. Accordingly, transferring the underlying technology to other cell systems or process modes, still typically requires a significant adaptation of the MBR design-which often necessitates complex manufacturing steps.Īdditive manufacturing (also known as 3D printing) has become a focus of interest for a variety of biotechnological applications in recent years. Importantly, however, all of these systems are prototypes developed specifically for use in their respective applications. cerevisiae 11 and chemostat mode with Staphyllococcus carnosus 12. The functionality and the high potential of the cuvette MBR has been demonstrated for cultivation in batch mode with S. A cuvette MBR with online sensor technology for pH, OD, DOT, and glucose measurements was also recently developed 11. The ♛C was numerically simulated with respect to its mass transfer and mixing behaviour by means of Computational Fluid Dynamics (CFD) modelling, and was satisfactorily validated with experimental data. 10 manufactured a 60 µL microbubble column reactor (♛C) entirely from borosilicate glass (since the use of PDMS is only conditionally suitable for the production and use of MBR systems). A further MBR system resulted in a vertically operated, multi-phase bubble column microreactor, which allows an improved degassing of the cultivation medium 8, 9. ![]() 7 developed a 10 µL horizontal flow and passively gassed MBR system made of glass and PDMS with integrated online sensors for optical density (OD) and dissolved oxygen tension (DOT), which was used for the cultivation of Saccharomyces cerevisiae (S. This MBR technology allows researchers to obtain quantitative data concerning the most important process variables from a large number of simultaneously running cultivation approaches in real-time, with both high data density and accuracy 4– 6. Various MBR systems have been developed for automated and parallel operation to enable, e.g., a realistic scale up/down of biotechnological processes 1, characterization of mammalian cell heterogeneity 2, and the screening of whole cell and biotransformation systems 3. The presented 3D-♛CR shows enormous potential for experimental parallelization and enables a high level of flexibility in reactor design, which can support versatile process development.įor biopharmaceutical process development, microbioreactors (MBRs) with a cultivation volume ≤ 1000 µL play an essential role-especially for screening new production strains and/or process optimization. In order to quantify local flow patterns in the fluid, a three-dimensional and transient multiphase Computational Fluid Dynamics model was successfully developed and applied. By extensive comparison of different reactor designs, the influence of the geometry on the resulting hydrodynamics was investigated. The modular 3D-♛CR achieves rapid homogenization in less than 1 s and high oxygen transfer with k L a values up to 788 h −1 and is able to monitor biomass, pH, and DOT in the fluid phase, as well as CO 2 and O 2 in the gas phase. This study presents a customized 3D-printed micro bubble column reactor (3D-♛CR), which can be used for the cultivation of microorganisms (e.g., Saccharomyces cerevisiae) and allows online-monitoring of process parameters through integrated microsensor technology. Personalized experimental devices or entire bioreactors of high complexity can be manufactured within few hours from start to finish. With the technological advances in 3D printing technology, which are associated with ever-increasing printing resolution, additive manufacturing is now increasingly being used for rapid manufacturing of complex devices including microsystems development for laboratory applications. ![]()
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