Ejector loop reactors (ELR) are successfully used in industrial chemical processes for gas/liquid reactions. They achieve higher mass transfer rates compared to the stirred-tank reactor (STR) at comparable specific power input. Insufficient oxygen transport and shear stress induced growth inhibition are limiting parameters during microbial fermentation. Due to its better mass transfer characteristics, the ELR was expected to have beneficial effects on biomass and recombinant protein production. One concern, however, was whether the ELR's shear stress characteristics would have a negative effect. This study evaluated the suitability of using the Buss-Loop (R) Reactor (BLR), one of the most advanced ELR technologies, as a bioreactor. The well-studied STR was used as a reference. A lab scale BLR was adapted for microbial fermentation. Mass transfer rates and specific power inputs were within the same order of magnitude in the ELR and the reference STR. Maximum kLa values of 207 and 205 h(-1) at power inputs of 6.9 and 9.7 W/L were measured in the ELR and STR, respectively. During batch fermentation of Escherichia coli K12 MG1655, maximum cell densities were higher in the ELR (OD600 of 22) than in the STR (OD600 of 18). Green fluorescence protein (GFP) production with pGS1 was comparable; however, more GFP was released into the media in the ELR. This indicates higher cell disruption compared to the STR. Despite this drawback of the first prototype, our work clearly demonstrates the potential of the ELR as a system for microbial fermentations.

The use of continuous flow microreactors offers an interesting approach among the process intensification tools available. Fouling in a microreactor during synthesis of industrially relevant nanoparticles was investigated. In order to achieve this, microscale synthesis of phosphated TiO2 nanoparticles from titanium(IV) isopropoxide (TTIP) and titanium(IV) butoxide (TBUT) was employed. A continuous three step process, consisting of hydrolysis of the respective alkoxide, phosphate modification and precipitation was developed. The resulting catalyst was characterized by means of nitrogen adsorption, dynamic light scattering and SEM/EDX. It was observed that TM resulted in massive fouling, while a stable process was possible with TBUT. This was related to the nucleation time of the particles. The particle size directly after the critical hydrolysis step was investigated. The particles formed with MP as a precursor (3.4 nm) were larger than those obtained from TBUT (2.4 non). Diffusion based reactant concentration gradients within the multilamellar micromixer were calculated, and the corresponding Damkohler numbers for mixing were estimated to be 2.6.10(-3) for TBUT and 3.5.10(-2) for TTIP respectively. These numbers highlight the influence of incomplete mixing on fouling for TTIP as a precursor. Thus, our work demonstrates the necessity to consider the reaction kinetics during process intensification by miniaturization.

Streptavidin is a tetrameric protein with an extremely high affinity to biotin and different biotin-like peptide-tags. This characteristic causes its widespread use in biotechnology. Streptavidin is produced by the fermentation of wild type Streptomyces avidinii or by recombinant Streptomyces lavendulae, Escherichia coli, and Bacillus subtilis strains. However, little is known about the influence of power input and oxygen supply as well as feeding strategies on the production of streptavidin by S. avidinii. This paper provides a systematic analysis of the effect of rotary frequency of the stirrer, leading to a plateau-like streptavidin formation behaviour between 400 and 700 min−1. This plateau was characterized by specific power inputs between 79 and 107 W L−1 and corresponding maximal product concentrations of 6.90 μM in 6 days. Lower as well as higher rotary frequencies were not beneficial. Subsequently, a linear fed-batch procedure could be established reproducibly yielding 39.20 μM streptavidin in 14 days, characterized by a constant productivity of 114 nM h−1. Fed-batch procedures based on dissolved oxygen were less efficient. The linear feeding strategy presented in this paper led to the highest streptavidin concentration ever reported and exceeded the maximal product level given in the literature drastically by a factor of 8.5.

Enzymatic parameter determination is an essential step in biocatalytic process development. Therefore higher throughput in miniaturized devices is urgently needed. An ideal microfluidic device should combine easy immobilization and retention of a minimal amount of biocatalyst with a well-mixed reaction volume. Together, all criteria are hardly met by current tools. Here we describe a microfluidic reactor (mu MORE) which employs magnetic particles for both enzyme immobilization and efficient mixing using two permanent magnets placed in rotating cylinders next to the a glass chip reactor. The chip geometry and agitation speed was optimized by investigation of the mixing and retention characteristics using simulation and dye distribution analysis. Subsequently, the mu MORE was successfully applied to determine critical biocatalytic process parameters in a parallelized manner for the carboligation of benzaldehyde and acetaldehyde to (S)-2-hydroxy-1-phenylpropan-1-one with less than 5 mu g of benzoylformate decarboxylase from Pseudomonas putida immobilized on magnetic beads. Here, one run of the device in six parallelized glass reactors took only 2-3 h for an immobilized enzyme with very low activity (similar to 2 U/mg). The optimized parameter set was finally tested in a 10 mL enzyme membrane reactor, demonstrating that the mu MORE provides a solid data base for biocatalytic process optimization. (C) 2016 Elsevier B.V. All rights reserved.

The invention relates to an apparatus for mixing liquids in a micro channel (6) by means of magnetic particles (9) with a permanent magnet (1) which is moved by drive means so that the magnetic particles (9) transverse to the length of the microchannel (6 move), which are characterized in that it comprises two brackets (2) for receiving in each case at least one permanent magnet (1) which are provided with drive means connected, the movement of the permanent magnets (1, 1a enable), wherein between the supports (2) at least one micro-channel (6) is arranged such that a is located therein fluid flow between the holders (2) and wherein the drive means a movement of the permanent magnets (1, 1a) allowing out of the plane of the direction of flow of the liquid out ,

Chemie Ingenieur TechnikVolume 84, Issue 8 p. 1397-1397 PosterFree Access Entwicklung eines neuen Mikroreaktor-Konzepts für die enzymatische Carboligation D. Jussen, Corresponding Author D. Jussen jussendaniel@aol.com Forschungszentrum Jülich GmbH, IBG-1:Biotechnology, D-52425 Jülich, GermanyForschungszentrum Jülich GmbH, IBG-1:Biotechnology, D-52425 Jülich, GermanySearch for more papers by this authorProf. Dr. D. Valinger, Prof. Dr. D. Valinger University Zagreb, Faculty of Food Fechnology and Biotechnology, Pierottijeva 6, HR-10000 Zagreb, CroatiaSearch for more papers by this authorProf. Dr. M. Pohl, Prof. Dr. M. Pohl Forschungszentrum Jülich GmbH, IBG-1:Biotechnology, D-52425 Jülich, GermanySearch for more papers by this authorProf. Dr. W. Wiechert, Prof. Dr. W. Wiechert Forschungszentrum Jülich GmbH, IBG-1:Biotechnology, D-52425 Jülich, GermanySearch for more papers by this author D. Jussen, Corresponding Author D. Jussen jussendaniel@aol.com Forschungszentrum Jülich GmbH, IBG-1:Biotechnology, D-52425 Jülich, GermanyForschungszentrum Jülich GmbH, IBG-1:Biotechnology, D-52425 Jülich, GermanySearch for more papers by this authorProf. Dr. D. Valinger, Prof. Dr. D. Valinger University Zagreb, Faculty of Food Fechnology and Biotechnology, Pierottijeva 6, HR-10000 Zagreb, CroatiaSearch for more papers by this authorProf. Dr. M. Pohl, Prof. Dr. M. Pohl Forschungszentrum Jülich GmbH, IBG-1:Biotechnology, D-52425 Jülich, GermanySearch for more papers by this authorProf. Dr. W. Wiechert, Prof. Dr. W. Wiechert Forschungszentrum Jülich GmbH, IBG-1:Biotechnology, D-52425 Jülich, GermanySearch for more papers by this author First published: 25 July 2012 https://doi.org/10.1002/cite.201250390AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume84, Issue8Special Issue: ProcessNet-Jahrestagung 2012 und 30. Jahrestagung der BiotechnologenAugust, 2012Pages 1397-1397 ReferencesRelatedInformation

iii Abstract Process development poses one of the main bottlenecks during development of biocatalytic processes for fine and bulk chemicals. Therefore novel tools to decrease the cost of process development have come into the focus of interest. While modelling and small scale liquid handling in multi well based platforms are already employed, there is still a lack of continuous microfluidic reaction systems for enzyme process development. In this thesis the magnetic oscillation reactor for enzymes (μMORE), a novel continuous microfluidic reactor concept for process optimization has been developed. The system is mixed by magnetic beads, on which the enzyme is immobilized, by utilization of an oscillating magnetic field. The concept has been designed to allow for simple parallelization of multiple reactors. A six-fold enzyme microreactor system was constructed. The novel reactor system was developed, characterized and finally tested with benzoylformate decarboxylase from Pseudomonas putida. This enzyme catalyzes the carboligation of benzaldehyde and acetaldehyde to (S)-2-hydroxypropiophenone. The results indicate that the system provides a useful tool for enzyme process optimization, generating process parameters that are useful for scale up of the process from microto bench scale.