MAB - Biomolecular Separation Engineering

3D Printing and Process Analytical Technology (PAT)

For a safe use of Bioprinting in industrial settings the development of reliable and robust analytical methods is indispensable. To first understand and then control the printing process, it is important to investigate pre-printing phase, the actual printing process and the post-printing phase. A particular focus of our current research lies on analyzing the printing process by image-based methods. Via 2.5D and 3D image processing the printed objects are analyzed concerning their geometry and the exactness of print in comparison to the design. These methods can be used for the evaluation of the printability of different bioinks, for the estimation of the influence of manufacturing and process parameters as well as a promising tool for the printing process development.

Literature
2018
Gretzinger, S.; Beckert, N.; Gleadall, A.; Lee-Thedieck, C.; Hubbuch, J. (2018). 3D bioprinting – Flow cytometry as analytical strategy for 3D cell structures. Bioprinting, 11, e00023. doi:10.1016/j.BPRINT.2018.e00023

Hydrogels and Scaffolds

Hydrogels are gel-like to solid materials which consist mainly of water. Their three-dimensional structure is maintained by the chemical or physical interactions of a polymer network. The applications of hydrogels are widely spread in biotechnology. They serve as a support structure (scaffold) for cellular growth in the field of tissue engineering and for the immobilization of enzymes in the field of biotransformation. The use of stimulus-responsive gels as sensors and the use of protein-based hydrogels as so-called soft materials are also currently the subject of research projects. All of these applications have in common, that novel materials must first be developed, characterized and optimized with regard to their processability for 3D printing.

Literature
2020
Wenger, L.; Radtke, C. P.; Göpper, J.; Wörner, M.; Hubbuch, J. (2020). 3D-Printable and Enzymatically Active Composite Materials Based on Hydrogel-Filled High Internal Phase Emulsions. Frontiers in Bioengineering and Biotechnology, 8, Art. Nr.: 713. doi:10.3389/fbioe.2020.00713
2019
Peng, M.; Mittmann, E.; Wenger, L.; Hubbuch, J.; Engqvist, M. K. M.; Niemeyer, C. M.; Rabe, K. S. (2019). 3D‐Printed Phenacrylate Decarboxylase Flow Reactors for the Chemoenzymatic Synthesis of 4‐Hydroxystilbene. Chemistry - a European journal, 25 (70), 15998–16001. doi:10.1002/chem.201904206
2018
Maier, M.; Radtke, C. P.; Hubbuch, J.; Niemeyer, C. M.; Rabe, K. S. (2018). On-Demand Production of Flow-Reactor Cartridges by 3D Printing of Thermostable Enzymes. Angewandte Chemie / International edition, 57 (19), 5539–5543. doi:10.1002/anie.201711072
Radtke, C. P.; Hillebrandt, N.; Hubbuch, J. (2018). The Biomaker : An entry-level bioprinting device for biotechnological applications. Journal of chemical technology & biotechnology, 93 (3), 792–799. doi:10.1002/jctb.5429

Bioprinting & Cell handling

Bioprinting is a method for the manufacturing of 3D tissue-like structures (scaffolds) currently used in pharmaceutical and medical research. In order to translate these artificial tissues form research towards industrial applications as well as medical use, key issues need to be solved including biological (e.g. vascularisation), material sciences and process development aspects. Our group is currently focusing on the process development part of cell handling in the field of bioprinting. Including the supply of the cell material, the introduction of this biological material in so-called bio inks and their processing. Furthermore, we are engaged in the establishment of suitable methods for cell characterization of printed structures

Literature
2019
Gretzinger, S.; Limbrunner, S.; Hubbuch, J. (2019). Automated image processing as an analytical tool in cell cryopreservation for bioprocess development. Bioprocess and biosystems engineering, 42 (5), 665–675. doi:10.1007/s00449-019-02071-3
2018
Gretzinger, S.; Beckert, N.; Gleadall, A.; Lee-Thedieck, C.; Hubbuch, J. (2018). 3D bioprinting – Flow cytometry as analytical strategy for 3D cell structures. Bioprinting, 11, e00023. doi:10.1016/j.BPRINT.2018.e00023
Zimmermann, S.; Gretzinger, S.; Zimmermann, P. K.; Bogsnes, A.; Hansson, M.; Hubbuch, J. (2018). Cell Separation in Aqueous Two-Phase Systems − Influence of Polymer Molecular Weight and Tie-Line Length on the Resolution of Five Model Cell Lines. Biotechnology journal, 13 (2), Art. Nr.: 1700250. doi:10.1002/biot.201700250
2017
Zimmermann, S.; Scheeder, C.; Zimmermann, P. K.; Bogsnes, A.; Hansson, M.; Staby, A.; Hubbuch, J. (2017). High-throughput downstream process development for cell-based products using aqueous two-phase systems (ATPS) – A case study. Biotechnology journal, 12 (2), 1600587. doi:10.1002/biot.201600587
2016
Zimmermann, S.; Gretzinger, S.; Scheeder, C.; Schwab, M.-L.; Oelmeier, S. A.; Osberghaus, A.; Gottwald, E.; Hubbuch, J. (2016). High-throughput cell quantification assays for use in cell purification development - enabling technologies for cell production. Biotechnology journal, 11 (5), 676–686. doi:10.1002/biot.201500577