@misc{13475, abstract = {{In the context of data-driven bioprocess modeling, selecting appropriate regression models remains a critical challenge. This is especially the case when dealing with time-dependent process dynamics and complex measurement data. The practical relevance of this study lies in its critical assessment of the application constraints associated with multivariate linear regression models in bioprocess monitoring of cell culture processes. The applicability of Partial Least Squares and Ridge regression was evaluated for different cultivation phases. The results emphasize that no single linear modeling approach is universally suitable for capturing the complex behavior of mammalian cell cultures. This is why we present an enhanced segmented modeling approach by learning the optimal transition point from data and introducing a gradual model switch, allowing for smoother and more robust adaptation to process dynamics. This segmented model led to improved predictive performance compared to single-model regression across the entire process duration. Nevertheless, the heterogeneity of the 11 mammalian cell culture datasets used in this study posed significant challenges, with the best-performing models achieving prediction error of around 0.31 of the average offline viable cell density. These results underline the potential of phase-adaptive modeling, while also emphasizing the need for further optimization to robustly handle diverse bioprocess conditions.}}, author = {{Uhlendorff, Selina and Burankova, Tatsiana and Dahlmann, Katharina and Frahm, Björn and Pein-Hackelbusch, Miriam}}, booktitle = {{2025 International Workshop on Impedance Spectroscopy (IWIS)}}, isbn = {{979-8-3315-9323-0}}, keywords = {{cell culture, impedance spectroscopy, partial least squares, ridge regression}}, location = {{Chemnitz}}, pages = {{34--39}}, publisher = {{IEEE}}, title = {{{Application Constraints of Linear Multivariate Regression Models for Dielectric Spectroscopy in Inline Bioreactor Viable Cell Analysis}}}, doi = {{10.1109/iwis69004.2025.11339388}}, year = {{2026}}, } @misc{13651, author = {{Müller, Carolin and Alarinta, Jarmo and Frahm, Björn and Wirtanen, Gun}}, booktitle = {{SeAMK Journal}}, number = {{1}}, publisher = {{SeAMK}}, title = {{{Demonstration of Listeria innocua and Escherichia coli growth in ready-to-eat vegan foods}}}, volume = {{2}}, year = {{2025}}, } @inbook{13652, author = {{Hernández Rodríguez, Tanja and Frahm, Björn}}, booktitle = {{Digitale Zwillinge - Werkzeuge und Konzepte für intelligente Bioproduktion}}, editor = {{Herwig, Christoph and Pörtner, Ralf and Möller, Johannes}}, isbn = {{978-3-031-75697-9}}, pages = {{107--145}}, publisher = {{Springer }}, title = {{{Digitale Seed Train Zwillinge und statistische Methoden}}}, doi = {{doi.org/10.1007/978-3-031-75698-6}}, year = {{2025}}, } @misc{13653, author = {{Luttmann, Mario and Blome, André and Müller, Niklas and Naqvi, Syeda Khadeeja and Kutter, Alexander and Jekle, Mario and Müller, Ulrich and Frahm, Björn}}, location = {{Detmold, Germany}}, title = {{{Einblicke in die objektive Bewertung von Weizenbrötchen in der virtuellen Realität}}}, year = {{2025}}, } @misc{13654, author = {{Luttmann, Mario and Blome, André and Kutter, Alexander and Naqvi, Syeda Khadeeja and Müller, Niklas and Jekle, Mario and Frahm, Björn and Müller, Ulrich}}, location = {{Lemgo, Germany}}, title = {{{Qualitätskontrolle von Backwaren in der virtuellen Realität}}}, year = {{2025}}, } @misc{13655, author = {{Luttmann, Mario and Blome, André and Jekle, Mario and Frahm, Björn and Müller, Ulrich}}, location = {{Freising, Germany}}, title = {{{Weizenkleingebäck und Photogrammetrie: Einblicke in die bildbasierte Analyse von Backwaren}}}, year = {{2025}}, } @misc{13656, author = {{Luttmann, Mario and Blome, André and Segermann, Jan and Jekle, Mario and Frahm, Björn and Müller, Ulrich}}, location = {{Lemgo, Germany}}, title = {{{Erkenntnisse zur Nutzung von Photogrammetrie für die Untersuchung des Bräunungsverhaltens von Weizenbrötchen}}}, year = {{2025}}, } @misc{13657, author = {{Müller, Ulrich and Frahm, Björn and Blome, André and Luttmann, Mario}}, location = {{Detmold, Germany}}, title = {{{Teig 4.0}}}, year = {{2025}}, } @misc{13659, author = {{Blome, André and Luttmann, Mario and Frahm, Björn and Müller, Ulrich}}, location = {{Detmold, Germany}}, title = {{{Sensor-Retrofitting-System für den Einsatz in Lebensmittelherstellungsprozessen}}}, year = {{2025}}, } @misc{13660, author = {{Blome, André and Luttmann, Mario and Müller, Ulrich and Frahm, Björn}}, location = {{Detmold, Germany}}, title = {{{Erforschung geeigneter Sensortechnologien zur Erfassung qualitätsrelevanter Eigenschaften bei Sauerteigen}}}, year = {{2025}}, } @misc{13661, author = {{Luttmann, Mario and Blome, André and Frahm, Björn and Müller, Ulrich}}, location = {{Detmold, Germany}}, title = {{{Nutzung der Strangerweiterung zur Inline-Bewertung der viskoelastischen Eigenschaften von Weizenteigen}}}, year = {{2025}}, } @misc{13662, author = {{Luttmann, Mario and Blome, André and Müller, Ulrich and Frahm, Björn}}, location = {{Detmold, Germany}}, title = {{{Photogrammetrie als Mittel zur objektiven Qualitätserfassung von Backwaren}}}, year = {{2025}}, } @misc{13223, author = {{Uhlendorff, Selina and Burankova, Tatsiana and Dahlmann, Katharina and Frahm, Björn and Pein-Hackelbusch, Miriam}}, location = {{Chemnitz}}, title = {{{Application Constraints of Linear Multivariate Regression Models for Dielectric Spectroscopy in Inline Bioreactor Viable Cell Analysis}}}, year = {{2025}}, } @misc{13315, abstract = {{Determining cell density and viability with (semi‐)automated methods enables rapid cell cultivation analysis. However, scientific validation is required, typically by comparing results to manual counting. To address this, we present a method to evaluate and compare two cell counting methods exemplified by a manual and a semi‐automated method (Countstar BioTech). Experiments followed validation parameters aligned with the International Council for Harmonization (ICH) Q2(R1) guideline and a dilution series design based on ISO 20391‐2:2019. Both the semi‐automated and manual methods showed comparable specificity and linearity for Chinese hamster ovary (CHO)‐K1 cells. The semi‐automated method exhibited superior repeatability for total cell density, whereas cell viability results showed no significant difference.}}, author = {{Uhlendorff, Selina and Odefey, Ulrich and Frahm, Björn and Pein-Hackelbusch, Miriam}}, booktitle = {{Chemie Ingenieur Technik}}, issn = {{1522-2640}}, keywords = {{Cell density, Cell enumeration, Cell viability, CHO-K1}}, number = {{1-2}}, pages = {{57–68}}, publisher = {{Wiley}}, title = {{{Performance Comparison between Semi‐Automated and Manual Cell Counting for Animal Cell Culture}}}, doi = {{10.1002/cite.70048}}, volume = {{98}}, year = {{2025}}, } @misc{12021, author = {{Segermann, Jan and Luttmann, Mario and Blome, André and Feldt, Sebastian and Sivanesan, Sujee and Holst, Christoph-Alexander and Lohweg, Volker and Frahm, Björn and Müller, Ulrich}}, keywords = {{sourdough, fermentation, near-infrared spectroscopy, support vector machine}}, location = {{Lemgo}}, title = {{{Die Rolle von ML-Modellen in der Lebensmitteltechnologie: Eine Fallstudie zur Sauerteigfermentation mit NIR-Spektroskopie}}}, year = {{2024}}, } @misc{12022, author = {{Luttmann, Mario and Blome, André and Segermann, Jan and Jekle, Mario and Frahm, Björn and Müller, Ulrich}}, keywords = {{colorimetry, photogrammetry, wheat rolls, crust colour, 3D analysis}}, location = {{Lemgo}}, title = {{{Erkenntnisse zur Nutzung von Photogrammmetrie für die Untersuchung des Bräunungsverhaltens von Weizenbrötchen}}}, year = {{2024}}, } @misc{10957, author = {{Reinhardt, Lena and Gassenmeier, Veronika and Feldt, Sebastian and Plate, Sebastian and Tremmel, Martin and Frahm, Björn and Stosch, Martin}}, location = {{Recklinghausen}}, title = {{{Mycelium-based materials from residues of the regional wood industry}}}, year = {{2024}}, } @misc{12395, author = {{Müller, Carolin and Alarinta, Jarmo and Frahm, Björn and Wirtanen, Gun}}, location = {{Lemgo}}, title = {{{Investigation of microbial spoilage in vegan foods}}}, year = {{2024}}, } @misc{12396, author = {{Gassenmeier, Veronika and Campolongo, Giovanni and Frahm, Björn}}, location = {{Edinburgh, UK}}, title = {{{Dissolved Carbon Dioxide in Addition to Dissolved Oxygen for In-situ Monitoring of Hybridoma Cell Culture}}}, year = {{2024}}, } @misc{12397, author = {{Blome, André and Luttmann, Mario and Segermann, Jan and Jekle, Mario and Frahm, Björn and Müller, Ulrich}}, location = {{Recklinghausen, Germany}}, title = {{{Process optimization in baked goods production using inline sensors and objective product evaluation}}}, year = {{2024}}, } @unpublished{12400, abstract = {{Determining cell density and cell viability is fundamental for any cell cultivation process. In addition to the manual counting method using hemocytometers, (semi-)automated methods offer advantages such as lower variability and shortened analysis times. However, these methods should provide at least comparable results to the manual method, which is why a comparison of methods is essential. We conducted a dilution series experimental design according to ISO 20391-2:2019 and compared two cell counting methods based on validation parameters aligned with the ICH Q2(R1) guideline. Regarding specificity and linearity, the manual (hemocytometer) and semi-automated (Countstar BioTech®) method exhibited similar results in the two evaluated characteristics total cell density and cell viability of CHO-K1 cells. Regarding repeatability of determining total cell density, the semi-automated method achieved significant (α = 0.05) better results with average relative standard deviations of < 6 %, than the manual method with average relative standard deviations of > 9 %. Concerning repeatability of the cell viability measurement, no significant difference between the two methods were shown. These results show the suitabililty of the dilution series experimental design. For the applied example, they indicate that the investigated semi-automated method is an appropriate alternative to the manual method.}}, author = {{Ramm, Selina and Odefey, Ulrich and Frahm, Björn and Pein-Hackelbusch, Miriam}}, publisher = {{bioRxiv}}, title = {{{Semi-automated vs. manual: Comparative study of cell culture counting methods using validation parameters}}}, doi = {{10.1101/2024.05.30.596619}}, year = {{2024}}, } @misc{12402, abstract = {{In anaerobic technology, pH values are crucial for targeted volatile fatty acid production. While pH dynamics can be modeled using the Anaerobic Digestion Model No. 1 (ADM1), simulation results may be biased. To address this issue, the pH prediction routine of Visual Water, a specialized water chemistry simulator, was validated. Unlike ADM1, it accounts for ionic strength and activities while also providing an automated uncertainty analysis. The analysis revealed Visual Water simulations to better fit measured pH data from acidic solutions in a miniaturized stirred-tank reactor.}}, author = {{Kosse, Pascal and Hernández Rodriguez, Tanja and Frahm, Björn and Lübken, Manfred and Wichern, Marc}}, booktitle = {{Chemie Ingenieur Technik}}, issn = {{1522-2640}}, keywords = {{Anaerobic Digestion Model No. 1 (ADM1), Anaerobic technology, pH simulation, Uncertainty assessment, Visual Water}}, number = {{4}}, pages = {{528--534}}, publisher = {{Wiley}}, title = {{{Comparative Analysis of pH Prediction Routines in ADM1 and a Specialized Water Chemistry Simulator}}}, doi = {{10.1002/cite.202300188}}, volume = {{96}}, year = {{2024}}, } @misc{11378, author = {{Gassenmeier, Veronika and Campolongo, Giovanni and Frahm, Björn}}, location = {{Lyon, France}}, title = {{{Real-time Monitoring of DCO2 in addition to DO}}}, year = {{2023}}, } @misc{11381, author = {{Hernández Rodriguez, Tanja and Ramm, Selina and Lange-Hegermann, Markus and Frahm, Björn}}, location = {{Berlin, Germany}}, publisher = {{DECHEMA e.V.}}, title = {{{A systematic, model-based workflow for risk-based decision making in upstream development}}}, year = {{2023}}, } @misc{11382, author = {{Gassenmeier, Veronika and Kuhfuß, Fabian and Deppe, Sahar and Ifrim, George and Hernández Rodriguez, Tanja and Frahm, Björn}}, location = {{Recklinghausen, Germany}}, title = {{{View on a mechanistic model of Chlorella vulgaris in shake flasks}}}, year = {{2023}}, } @misc{11383, author = {{Hernández Rodriguez, Tanja and Posch, Christoph and Pörtner, Ralf and Lange-Hegermann, Markus and Wurm, Florian M. and Frahm, Björn}}, location = {{Berlin, Germany}}, publisher = {{DECHEMA e.V.}}, title = {{{Model-assisted design strategies for bioprocesses – Advanced statistical methods in industrial upstream cell culture}}}, year = {{2023}}, } @misc{11384, author = {{Müller, Carolin and Alarinta, Jarmo and Frahm, Björn and Wirtanen, Gun}}, booktitle = {{Proceedings of the 10th International Congress of Food Technologists, Biotechnologists and Nutritionists: Smart Food for a Healthy Planet and Human Prosperity}}, issn = {{2975-7118}}, location = {{Zagreb}}, pages = {{64 – 67}}, publisher = {{Croatian Society of Food Technologists, Biotechnologists and Nutritionists, Zagreb, Croatia, Editors: Draženka Komes, Sanja Vidaček Filipec and Bojana Voučko}}, title = {{{Microbial spoilage in vegan foods}}}, year = {{2023}}, } @misc{11385, abstract = {{Accurate pH calculations are essential for scientists across different disciplines to design optimal reactor solutions, but they can be arduous to calculate for complex acid-base solutions. Visual Water is a powerful software tool that provides accurate pH calculations with automated mathematical uncertainty analysis. Its workflow is presented and validated using acids and bases, showing a deviation of < 0.2 pH units between measured and calculated pH values. This highlights the software's reliability, which can help to simplify the work of non-experts in water chemistry.}}, author = {{Kosse, Pascal and Hernández Rodriguez, Tanja and Frahm, Björn and Lübken, Manfred and Wichern, Marc}}, booktitle = {{Chemie Ingenieur Technik}}, issn = {{1522-2640}}, keywords = {{Acid-base equilibria, Carboxylic acids, Dissociation constants, pH calculation software, Uncertainty assessment}}, number = {{12}}, pages = {{1960--1969}}, publisher = {{Wiley}}, title = {{{Validation and Uncertainty Assessment of a Software‐Integrated Workflow for pH Calculations}}}, doi = {{10.1002/cite.202300082}}, volume = {{95}}, year = {{2023}}, } @misc{11487, author = {{Ramm, Selina and Hernández Rodriguez, Tanja and Frahm, Björn and Pein-Hackelbusch, Miriam}}, location = {{Berlin, Germany}}, publisher = {{DECHEMA e.V.}}, title = {{{Comparison of Preprocessing Methods of Dielectric Spectroscopy Data and the Effects on Linear Regression }}}, year = {{2023}}, } @misc{13650, author = {{Uhlendorff, Selina and Hernández Rodríguez, Tanja and Frahm, Björn and Pein-Hackelbusch, Miriam}}, location = {{Lemgo, Germany}}, title = {{{Systematic Preprocessing of Dielectric Spectroscopy Data and Estimating Viable Cell Densities}}}, year = {{2023}}, } @misc{10201, author = {{Hernández Rodriguez, Tanja and Ramm, Selina and Lange-Hegermann, Markus and Frahm, Björn}}, location = {{Recklinghausen, Germany}}, title = {{{A systematic, model-based workflow for risk-based decision making in upstream development}}}, year = {{2023}}, } @misc{10788, abstract = {{For process monitoring, an adequate data preprocessing is crucial to link accessible inline process data with offline measured target variables. Literature, however, does not provide systematic preprocessing strategies. The effects of five different preprocessing strategies on data from a Dielectric Spectroscopy system applied to the Viable Cell Density (VCD) of a mammalian cell cultivation were thus evaluated. Single-frequency measurements are typically used to model the VCD over the growth phase using linear regression or the Cole-Cole model and served as a reference. As multi-frequency measurement is promising to model the VCD beyond the growth phase using Partial Least Squares Regression (PLSR), we further aimed to determine, whether replacing linear regression by PLSR shows comparable modeling performance. All five preprocessing strategies led to comparable results. Exemplary, when using capacitance values at a frequency of 3347 kHz, linear regression resulted in a R2 of 0.90 and a standard deviation of 0.4 % on average. Both normalization techniques had the same positive effect on the results of PLSR. The order of smoothing and normalization was irrelevant for both regression methods. Comparing the results of linear regression and PLSR, the latter obtained on average 9 % better results. Therefore, we concluded that PLSR is preferable over linear regression and is potentially suitable to model the VCD beyond the growth phase, which is suggested to be investigated based on more data sets.}}, author = {{Ramm, Selina and Hernández Rodriguez, Tanja and Frahm, Björn and Pein-Hackelbusch, Miriam}}, booktitle = {{2023 IEEE 21st International Conference on Industrial Informatics (INDIN)}}, editor = {{Jasperneite, Jürgen and Wisniewski, Lukasz and Fung Man, Kim}}, isbn = {{978-1-6654-9314-7}}, issn = {{1935-4576}}, keywords = {{Spectroscopy, Smoothing methods, Systematics, Phase measurement, Linear regression, Data models, Dielectric measurement}}, location = {{Lemgo}}, pages = {{1--6}}, publisher = {{IEEE}}, title = {{{Systematic Preprocessing of Dielectric Spectroscopy Data and Estimating Viable Cell Densities}}}, doi = {{10.1109/INDIN51400.2023.10218012}}, year = {{2023}}, } @misc{11109, author = {{Blome, André and Luttmann, Mario and Jekle, Mario and Frahm, Björn and Müller, Ulrich}}, location = {{Bochum}}, title = {{{Untersuchung der räumlichen Verteilung von viskoelastischen Kenngrößen während der Weizenteigbereitung}}}, year = {{2023}}, } @misc{11110, author = {{Blome, André and Luttmann, Mario and Segermann, Jan and Jekle, Mario and Frahm, Björn and Müller, Ulrich}}, location = {{Bochum}}, title = {{{Vorstellung des Projektes „Teig 4.0“ - Prozessoptimierung im Bereich der industriellen Weizenteigverarbeitung}}}, year = {{2023}}, } @misc{12483, author = {{Blome, André and Luttmann, Mario and Segermann, Jan and Jekle, Mario and Frahm, Björn and Müller, Ulrich}}, location = {{Lemgo, Germany}}, title = {{{Vorstellung des Projektes „Teig 4.0“ - Prozessoptimierung im Bereich der industriellen Weizenteigverarbeitung}}}, year = {{2023}}, } @misc{12485, author = {{Luttmann, Mario and Blome, André and Jekle, Mario and Frahm, Björn and Müller, Ulrich}}, location = {{Lemgo, Germany}}, title = {{{Teig 4.0 - Promotionsthemen}}}, year = {{2023}}, } @misc{7932, author = {{Hernández Rodriguez, Tanja and Ramm, Selina and Lange-Hegermann, Markus and Frahm, Björn}}, location = {{Barcelona, Spain}}, title = {{{A systematic, model-based workflow for risk-based decision making in upstream development}}}, year = {{2022}}, } @misc{7976, author = {{Gassenmeier, Veronika and Deppe, Sahar and Hernández Rodriguez, Tanja and Kuhfuß, Fabian and Moser, André and Hass, Volker C. and Kuchemüller, Kim B. and Pörtner, Ralf and Möller, Johannes and Ifrim, George Adrian and Frahm, Björn}}, booktitle = {{Current Research in Biotechnology}}, issn = {{2590-2628 }}, pages = {{102--119}}, publisher = {{Elsevier}}, title = {{{Model-assisted DoE applied to microalgae processes, Current Research in Biotechnology}}}, doi = {{10.1016/j.crbiot.2022.01.005}}, volume = {{4}}, year = {{2022}}, } @misc{7977, abstract = {{Kinetic growth models are a useful tool for a better understanding of microalgal cultivation and for optimizing cultivation conditions. The evaluation of such models requires experimental data that is laborious to generate in bioreactor settings. The experimental shake flask setting used in this study allows to run 12 experiments at the same time, with 6 individual light intensities and light durations. This way, 54 biomass data sets were generated for the cultivation of the microalgae Chlorella vulgaris. To identify the model parameters, a stepwise parameter estimation procedure was applied. First, light-associated model parameters were estimated using additional measurements of local light intensities at differ heights within medium at different biomass concentrations. Next, substrate related model parameters were estimated, using experiments for which biomass and nitrate data were provided. Afterwards, growth-related model parameters were estimated by application of an extensive cross validation procedure.}}, author = {{Kuhfuß, Fabian and Gassenmeier, Veronika and Deppe, Sahar and Ifrim, George Adrian and Hernández Rodriguez, Tanja and Frahm, Björn}}, booktitle = {{Bioprocess and Biosystems Engineering}}, issn = {{1615-7605}}, pages = {{15--30}}, publisher = {{Springer}}, title = {{{View on a mechanistic model of Chlorella vulgaris in incubated shake flasks}}}, doi = {{10.1007/s00449-021-02627-2}}, volume = {{45}}, year = {{2022}}, } @misc{11377, abstract = {{consuming and often performed rather empirically. Efficient optimization of multiple objectives such as process time, viable cell density, number of operating steps & cultivation scales, required medium, amount of product as well as product quality depicts a promising approach. This contribution presents a workflow which couples uncertainty-based upstream simulation and Bayes optimization using Gaussian processes. Its application is demonstrated in a simulation case study for a relevant industrial task in process development, the design of a robust cell culture expansion process (seed train), meaning that despite uncertainties and variabilities concerning cell growth, low variations of viable cell density during the seed train are obtained. Compared to a non-optimized reference seed train, the optimized process showed much lower deviation rates regarding viable cell densities (<10% instead of 41.7%) using five or four shake flask scales and seed train duration could be reduced by 56 h from 576 h to 520 h. Overall, it is shown that applying Bayes optimization allows for optimization of a multi-objective optimization function with several optimizable input variables and under a considerable amount of constraints with a low computational effort. This approach provides the potential to be used in the form of a decision tool, e.g., for the choice of an optimal and robust seed train design or for further optimization tasks within process development.}}, author = {{Hernández Rodriguez, Tanja and Sekulic, Anton and Lange-Hegermann, Markus and Frahm, Björn}}, booktitle = {{Processes}}, issn = {{2227-9717}}, keywords = {{Gaussian processes, Bayes optimization, Pareto optimization, multi-objective, cell culture, seed train}}, number = {{5}}, publisher = {{MDPI AG}}, title = {{{Designing Robust Biotechnological Processes Regarding Variabilities Using Multi-Objective Optimization Applied to a Biopharmaceutical Seed Train Design}}}, doi = {{10.3390/pr10050883}}, volume = {{10}}, year = {{2022}}, } @misc{10190, author = {{Gassenmeier, Veronika and Frahm, Björn}}, publisher = {{assets-labs}}, title = {{{Real-time Monitoring of DCO2 in addition to DO}}}, year = {{2022}}, } @inbook{10193, abstract = {{Development and optimization of biopharmaceutical production processes with cell cultures is cost- and time-consuming and often performed rather empirically. Efficient optimization of multiple objectives such as process time, viable cell density, number of operating steps & cultivation scales, required medium, amount of product as well as product quality depicts a promising approach. This contribution presents a workflow which couples uncertainty-based upstream simulation and Bayes optimization using Gaussian processes. Its application is demonstrated in a simulation case study for a relevant industrial task in process development, the design of a robust cell culture expansion process (seed train), meaning that despite uncertainties and variabilities concerning cell growth, low variations of viable cell density during the seed train are obtained. Compared to a non-optimized reference seed train, the optimized process showed much lower deviation rates regarding viable cell densities (<10% instead of 41.7%) using five or four shake flask scales and seed train duration could be reduced by 56 h from 576 h to 520 h. Overall, it is shown that applying Bayes optimization allows for optimization of a multi-objective optimization function with several optimizable input variables and under a considerable amount of constraints with a low computational effort. This approach provides the potential to be used in the form of a decision tool, e.g., for the choice of an optimal and robust seed train design or for further optimization tasks within process development.}}, author = {{Hernández Rodriguez, Tanja and Sekulic, Anton and Lange-Hegermann, Markus and Frahm, Björn}}, booktitle = {{Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing}}, editor = {{Pörtner, Ralf and Möller, Johannes}}, isbn = {{978-3-0365-5210-1}}, issn = {{2227-9717}}, keywords = {{Gaussian processes, Bayes optimization, Pareto optimization, multi-objective, cell culture, seed train}}, pages = {{21--48}}, publisher = {{MDPI}}, title = {{{Designing robust biotechnological processes regarding variabilities using multi-objective optimization applied to a biopharmaceutical seed train design}}}, doi = {{https://doi.org/10.3390/pr10050883}}, volume = {{special issue}}, year = {{2022}}, } @misc{10195, author = {{Blome, André and Luttmann, Mario and Segermann, Jan and Jekle, Mario and Frahm, Björn and Müller, Ulrich}}, booktitle = {{Proceedings of the 33rd VH Yeast Conference 2022: Advances in Applied Research & Industrial Production of Baker’s Yeast, “100th anniversary of VH Berlin & Yeast(s) as an alternative protein source”}}, location = {{Berlin, Germany}}, pages = {{61 -- 66}}, publisher = {{Versuchsanstalt der Hefeindustrie e.V.}}, title = {{{Process optimisation in the field of wheat dough processing using real-time recording of quality-relevant characteristics in raw materials, intermediates and final products}}}, year = {{2022}}, } @misc{10196, author = {{Blome, André and Luttmann, Mario and Segermann, Jan and Jekle, Mario and Frahm, Björn and Müller, Ulrich}}, location = {{Berlin, Germany}}, title = {{{Process optimisation in the field of wheat dough processing using real-time recording of quality-relevant characteristics in raw materials, intermediates and final products}}}, year = {{2022}}, } @misc{10197, author = {{Hernández Rodriguez, Tanja and Posch, Christoph and Pörtner, Ralf and Frahm, Björn}}, booktitle = {{ACHEMA 2022}}, location = {{Frankfurt am Main, Germany}}, title = {{{Model assisted Design Strategies for Bioprocesses – Advanced statistical methods in industrial upstream cell culture}}}, year = {{2022}}, } @misc{10198, author = {{Hernández Rodriguez, Tanja and Pörtner, Ralf and Lange-Hegermann, Markus and Wurm, Florian M. and Frahm, Björn}}, location = {{Lisbon, Portugal }}, title = {{{A systematic, model-based approach for decision making in upstream development – Considerations regarding clone selection and cell expansion}}}, year = {{2022}}, } @misc{10199, author = {{Müller, Carolin and Alarinta, Jarmo and Frahm, Björn and Wirtanen, Gun}}, booktitle = {{PBN 2022 Congress}}, location = {{Zagreb, Croatia}}, title = {{{Microbial spoilage in vegan foods}}}, year = {{2022}}, } @misc{7927, author = {{Hernández Rodriguez, Tanja and Frahm, Björn}}, location = {{SeAMK, Seinäjoki, Finnland}}, title = {{{Model-based methods in bioprocess technology - Bioprocess modeling, simulation and prediction}}}, year = {{2021}}, } @misc{7931, author = {{Moser, André and Möller, Johannes and Kuchemüller, Kim B. and Deppe, Sahar and Hernández Rodriguez, Tanja and Gassenmeier, Veronika and Ifrim, George Adrian and Frahm, Björn and Pörtner, Ralf and Hass, Volker C.}}, location = {{as a web conference, Prague, Czech Republic}}, title = {{{Model-assisted Design of Experiments - Concept, Software and Applications}}}, year = {{2021}}, } @misc{7939, author = {{Wirtanen, Gun and Alarinta, Jarmo and Frahm, Björn and Fasse, Sylvia}}, booktitle = {{MDPI Encyclopedia, Scholarly Community Encyclopedia, Category: Agriculture, Dairy & Animal Science}}, title = {{{Bovine Colostrum for Human Consumption}}}, year = {{2021}}, } @misc{7981, abstract = {{The main purpose of bovine colostrum, being the milk secreted by a cow after giving birth, is to transfer passive immunity to the calf. The calves have an immature immune system as they lack immunoglobulins (Igs). Subsequently, the supply of good quality bovine colostrum is required. The quality of colostrum is classified by low bacterial counts and adequate Ig concentrations. Bacterial contamination can contain a variety of human pathogens or high counts of spoilage bacteria, which has become more challenging with the emerging use of bovine colostrum as food and food supplements. There is also a growing risk for the spread of zoonotic diseases originating from bovines. For this reason, processing based on heat treatment or other feasible techniques is required. This review provides an overview of literature on the microbial quality of bovine colostrum and processing methods to improve its microbial quality and keep its nutritional values as food. The highlights of this review are as follows: high quality colostrum is a valuable raw material in food products and supplements; the microbial safety of bovine colostrum is increased using an appropriate processing-suitable effective heat treatment which does not destroy the high nutrition value of colostrum; the heat treatment processes are cost-effective compared to other methods; and heat treatment can be performed in both small- and large-scale production.}}, author = {{Fasse, Sylvia and Alarinta, Jarmo and Frahm, Björn and Wirtanen, Gun}}, booktitle = {{Dairy}}, issn = {{2624-862X }}, keywords = {{bovine colostrum, bacteria, pathogens, probiotic bacteria, cost-effective processing, heat treatment, pasteurization, contamination control, immunoglobulins, enzymes}}, number = {{4}}, pages = {{556--575}}, publisher = {{MDPI}}, title = {{{Bovine Colostrum for Human Consumption - Improving Microbial Quality and Maintaining Bioactive Characteristics through Processing}}}, doi = {{10.3390/dairy2040044}}, volume = {{2}}, year = {{2021}}, } @inbook{7983, abstract = {{For the manufacturing of complex biopharmaceuticals using bioreactors with cultivated mammalian cells, high product concentration is an important objective. The phenotype of the cells in a reactor plays an important role. Are clonal cell populations showing high cell-specific growth rates more favorable than cell lines with higher cell-specific productivities or vice versa? Five clonal Chinese hamster ovary cell populations were analyzed based on the data of a 3-month-stability study. We adapted a mechanistic cell culture model to the experimental data of one such clonally derived cell population. Uncertainties and prior knowledge concerning model parameters were considered using Bayesian parameter estimations. This model was used then to define an inoculum train protocol. Based on this, we subsequently simulated the impacts of differences in growth rates (±10%) and production rates (±10% and ±50%) on the overall cultivation time, including making the inoculum train cultures; the final production phase, the volumetric titer in that bioreactor and the ratio of both, defined as overall process productivity. We showed thus unequivocally that growth rates have a higher impact (up to three times) on overall process productivity and for product output per year, whereas cells with higher productivity can potentially generate higher product concentrations in the production vessel.}}, author = {{Hernández Rodriguez, Tanja and Morerod, Sophie and Pörtner, Ralf and Wurm, Florian M. and Frahm, Björn}}, booktitle = {{Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing}}, isbn = {{978-3-0365-5210-1}}, issn = {{2227-9717 }}, keywords = {{clonal cell population, phenotypic diversity, inoculum train, uncertainty-based, cell culture model, biopharmaceutical manufacturing}}, pages = {{49--74}}, publisher = {{MDPI}}, title = {{{Considerations of the impacts of cell-specific growth and production rate on clone selection – a simulation study}}}, doi = {{10.3390/pr9060964}}, volume = {{special issue}}, year = {{2021}}, } @misc{11376, abstract = {{concentration is an important objective. The phenotype of the cells in a reactor plays an important role. Are clonal cell populations showing high cell-specific growth rates more favorable than cell lines with higher cell-specific productivities or vice versa? Five clonal Chinese hamster ovary cell populations were analyzed based on the data of a 3-month-stability study. We adapted a mechanistic cell culture model to the experimental data of one such clonally derived cell population. Uncertainties and prior knowledge concerning model parameters were considered using Bayesian parameter estimations. This model was used then to define an inoculum train protocol. Based on this, we subsequently simulated the impacts of differences in growth rates (±10%) and production rates (±10% and ±50%) on the overall cultivation time, including making the inoculum train cultures; the final production phase, the volumetric titer in that bioreactor and the ratio of both, defined as overall process productivity. We showed thus unequivocally that growth rates have a higher impact (up to three times) on overall process productivity and for product output per year, whereas cells with higher productivity can potentially generate higher product concentrations in the production vessel.}}, author = {{Hernández Rodriguez, Tanja and Morerod, Sophie and Pörtner, Ralf and Wurm, Florian M. and Frahm, Björn}}, booktitle = {{Processes}}, issn = {{2227-9717}}, keywords = {{clonal cell population, phenotypic diversity, inoculum train, uncertainty-based, cell culture model, biopharmaceutical manufacturing}}, number = {{6}}, publisher = {{MDPI AG}}, title = {{{Considerations of the Impacts of Cell-Specific Growth and Production Rate on Clone Selection—A Simulation Study}}}, doi = {{10.3390/pr9060964}}, volume = {{9}}, year = {{2021}}, } @misc{7985, abstract = {{Bioprocess modeling has become a useful tool for prediction of the process future with the aim to deduce operating decisions (e.g. transfer or feeds). Due to variabilities, which often occur between and within batches, updating (re-estimation) of model parameters is required at certain time intervals (dynamic parameter estimation) to obtain reliable predictions. This can be challenging in the presence of low sampling frequencies (e.g. every 24 h), different consecutive scales and large measurement errors, as in the case of cell culture seed trains. This contribution presents an iterative learning workflow which generates and incorporates knowledge concerning cell growth during the process by using a moving horizon estimation (MHE) approach for updating of model parameters. This estimation technique is compared to a classical weighted least squares estimation (WLSE) approach in the context of model updating over three consecutive cultivation scales (40–2160 L) of an industrial cell culture seed train. Both techniques were investigated regarding robustness concerning the aforementioned challenges and the required amount of experimental data (estimation horizon). It is shown how the proposed MHE can deal with the aforementioned difficulties by the integration of prior knowledge, even if only data at two sampling points are available, outperforming the classical WLSE approach. This workflow allows to adequately integrate current process behavior into the model and can therefore be a suitable component of a digital twin.}}, author = {{Hernández Rodriguez, Tanja and Posch, Christoph and Pörtner, Ralf and Frahm, Björn}}, booktitle = {{Bioprocess and Biosystems Engineering}}, issn = {{1615-7605}}, keywords = {{Dynamic parameter estimation, Bioprocess, Cell cultures, Moving horizon estimation, Prior knowledge}}, number = {{4}}, pages = {{793--808}}, publisher = {{Springer}}, title = {{{Dynamic parameter estimation and prediction over consecutive scales, based on moving horizon estimation - applied to an industrial cell culture seed train}}}, doi = {{10.1007/s00449-020-02488-1 }}, volume = {{44}}, year = {{2021}}, } @misc{7986, abstract = {{Bioprocess development and optimization are still cost- and time-intensive due to the enormous number of experiments involved. In this study, the recently introduced model-assisted Design of Experiments (mDoE) concept (Möller et al. in Bioproc Biosyst Eng 42(5):867, https://doi.org/10.1007/s00449-019-02089-7, 2019) was extended and implemented into a software (“mDoE-toolbox”) to significantly reduce the number of required cultivations. The application of the toolbox is exemplary shown in two case studies with Saccharomyces cerevisiae. In the first case study, a fed-batch process was optimized with respect to the pH value and linearly rising feeding rates of glucose and nitrogen source. Using the mDoE-toolbox, the biomass concentration was increased by 30% compared to previously performed experiments. The second case study was the whole-cell biocatalysis of ethyl acetoacetate (EAA) to (S)-ethyl-3-hydroxybutyrate (E3HB), for which the feeding rates of glucose, nitrogen source, and EAA were optimized. An increase of 80% compared to a previously performed experiment with similar initial conditions was achieved for the E3HB concentration.}}, author = {{Moser, André and Kuchemüller, Kim B. and Deppe, Sahar and Hernández Rodriguez, Tanja and Frahm, Björn and Pörtner, Ralf and Hass, Volker C. and Möller, Johannes}}, booktitle = {{Bioprocess and Biosystems Engineering}}, isbn = {{1615-7591}}, issn = {{1615-7605}}, keywords = {{Biocatalysis, Monte Carlo methods, Fed-batch strategy, Model-assisted design of experiments, Quality by design}}, number = {{4}}, pages = {{683--700}}, publisher = {{Springer}}, title = {{{Model-assisted DoE software: Optimization of growth and biocatalysis in Saccharomyces cerevisiae bioprocesses}}}, doi = {{10.1007/s00449-020-02478-3}}, volume = {{44}}, year = {{2021}}, } @misc{8078, author = {{Blome, André and Luttmann, Mario and Frahm, Björn and Müller, Ulrich}}, booktitle = {{Seminar Life Science Technologies 2021-04-28}}, location = {{Lemgo, Germany}}, title = {{{Messtechnikkonzepte für die Erfassung von qualitätsrelevanten Parametern und Merkmalen bei der Weizenteigverarbeitung}}}, year = {{2021}}, } @inbook{3349, abstract = {{Model-based concepts and simulation techniques in combination with digital tools emerge as a key to explore the full potential of biopharmaceutical production processes, which contain several challenging development and process steps. One of these steps is the time- and cost-intensive cell proliferation process (also called seed train) to increase cell number from cell thawing up to production scale. Challenges like complex cell metabolism, batch-to-batch variation, variabilities in cell behavior, and influences of changes in cultivation conditions necessitate adequate digital solutions to provide information about the current and near future process state to derive correct process decisions. For this purpose digital seed train twins have proved to be efficient, which digitally display the time-dependent behavior of important process variables based on mathematical models, strategies, and adaption procedures. This chapter will outline the needs for digitalization of seed trains, the construction of a digital seed train twin, the role of parameter estimation, and different statistical methods within this context, which are applicable to several problems in the field of bioprocessing. The results of a case study are presented to illustrate a Bayesian approach for parameter estimation and prediction of an industrial cell culture seed train for seed train digitalization.}}, author = {{Hernández Rodriguez, Tanja and Frahm, Björn}}, booktitle = {{Digital Twins Tools and Concepts for Smart Biomanufacturing}}, editor = {{Herwig, Christoph and Pörtner, Ralf and Möller, Johannes }}, isbn = {{978-3-030-71659-2}}, issn = {{1616-8542}}, keywords = {{Bayes, Digital twin, Parameter estimation, Seed train, Uncertainty}}, pages = {{97–131}}, publisher = {{Springer}}, title = {{{Digital Seed Train Twins and Statistical Methods}}}, doi = {{https://doi.org/10.1007/10_2020_137}}, volume = {{176}}, year = {{2021}}, } @misc{7929, author = {{Hernández Rodriguez, Tanja and Deppe, Sahar and Gassenmeier, Veronika and Kuhfuß, Fabian and Tölle, Marius and Ifrim, George Adrian and Frahm, Björn}}, location = {{als Web-Konferenz, Aachen, Germany}}, title = {{{Modeling of Chlorella vulgaris in shake flasks with respect to light intensity and light duration}}}, year = {{2020}}, } @misc{7930, author = {{Hernández Rodriguez, Tanja and Posch, Christoph and Pörtner, Ralf and Frahm, Björn}}, location = {{als Web-Konferenz, Aachen, Germany}}, title = {{{Towards integration of prior knowledge and propagation of uncertainty for digital twins of biopharmaceutical production processes}}}, year = {{2020}}, } @misc{7936, author = {{Hernández Rodriguez, Tanja and Frahm, Björn and Posch, Christoph}}, location = {{Sandoz, Austria}}, title = {{{Integration of prior knowledge and digital tools for uncertainty-based decision support}}}, year = {{2020}}, } @misc{7937, author = {{Hernández Rodriguez, Tanja and Deppe, Sahar and Gassenmeier, Veronika and Kuhfuß, Fabian and Tölle, Marius and Ifrim, George Adrian and Frahm, Björn}}, booktitle = {{Chemie Ingenieur Technik, Tagungsband zur 10. ProcessNet-Jahrestagung und 34. DECHEMA-Jahrestagung der Biotechnologen 2020}}, pages = {{1225 – 1226}}, publisher = {{Wiley}}, title = {{{Modeling of Chlorella vulgaris algae in shake flasks with respect to light intensity and light duration}}}, doi = {{10.1002/cite.202055235}}, volume = {{No. 9}}, year = {{2020}}, } @misc{7938, author = {{Hernández Rodriguez, Tanja and Posch, Christoph and Pörtner, Ralf and Frahm, Björn}}, booktitle = {{Chemie Ingenieur Technik, Tagungsband zur 10. ProcessNet-Jahrestagung und 34. DECHEMA-Jahrestagung der Biotechnologen 2020}}, pages = {{1241 – 1242}}, publisher = {{Wiley}}, title = {{{Towards integration of prior knowledge and propagation of uncertainty for digital twins of biopharmaceutical production processes}}}, doi = {{10.1002/cite.202055234}}, volume = {{No. 9}}, year = {{2020}}, } @misc{2392, author = {{Möller, Johannes and Hernández Rodríguez, Tanja and Müller, Jan and Arndt, Lukas and Kuchemüller, Kim B. and Frahm, Björn and Eibl, Regine and Eibl, Dieter and Pörtner, Ralf}}, booktitle = {{Computers & Chemical Engineering}}, issn = {{0098-1354}}, pages = {{1--13}}, publisher = {{Elsevier}}, title = {{{Model uncertainty-based evaluation of process strategies during scale-up of biopharmaceutical processes}}}, doi = {{10.1016/j.compchemeng.2019.106693}}, volume = {{134}}, year = {{2020}}, } @inbook{2397, author = {{Hernández Rodríguez, Tanja and Frahm, Björn}}, booktitle = {{Animal Cell Biotechnology - Methods and Protocols}}, editor = {{Pörtner, Ralf}}, isbn = {{978-1-07-160190-7}}, issn = {{1064-3745}}, pages = {{251--267}}, publisher = {{Springer}}, title = {{{Design, Optimization and Adaptive Control of Cell Culture Seed Trains}}}, doi = {{10.1007/978-1-0716-0191-4_14}}, volume = {{2095}}, year = {{2020}}, } @inbook{2399, author = {{Deppe, S. and Frahm, Björn and Hass, V. C. and Hernández Rodríguez, T. and Kuchemüller, K. B. and Möller, J. and Pörtner, R.}}, booktitle = {{Animal Cell Biotechnology: Methods and Protocols}}, editor = {{Pörtner, Ralf}}, isbn = {{978-1-07-160190-7}}, issn = {{1064-3745}}, pages = {{213--234}}, publisher = {{Springer}}, title = {{{Estimation of Process Model Parameters}}}, doi = {{10.1007/978-1-0716-0191-4_12}}, volume = {{2095}}, year = {{2020}}, } @misc{2822, author = {{Hernández Rodriguez, Tanja and Posch, Christoph and Schmutzhard, Julia and Stettner, Josef and Weihs, Claus and Pörtner, Ralf and Frahm, Björn}}, booktitle = {{BMC Proceedings}}, issn = {{1753-6561}}, location = {{Copenhagen, Denmark.}}, pages = {{P408}}, publisher = {{BioMed Central}}, title = {{{Predicting Industrial Cell Culture Seed Trains - A Bayesian Approach}}}, doi = {{10.1186/s12919-020-00188-y}}, volume = {{14}}, year = {{2020}}, } @misc{3007, author = {{Kuhfuß, F. and Tölle, M. and Hernández Rodriguez, Tanja and Gassenmeier, Veronika and Deppe, S. and Ifrim, George Adrian and Frahm, Björn}}, location = {{Recklinghausen, Germany}}, title = {{{Modeling of Chlorella vulgaris in shake flasks with respect to light intensity and light duration}}}, year = {{2020}}, } @misc{3008, author = {{Deppe, S. and Kuhfuß, F. and Tölle, M. and Hernández Rodriguez, Tanja and Gassenmeier, Veronika and Ifrim, George Adrian and Möller, J. and Pörtner, R. and Moser, A. and Hass, V. C. and Frahm, Björn}}, location = {{Recklinghausen, Germany}}, title = {{{Model-assisted Design of Experiments for algae cultivation}}}, year = {{2020}}, } @misc{3009, author = {{Ifrim, George Adrian and Deppe, S. and Hernández Rodriguez, Tanja and Gassenmeier, Veronika and Frahm, Björn}}, location = {{Recklinghausen, Germany}}, title = {{{Modeling of microalgae in an air-lift photobioreactor for biomass production}}}, year = {{2020}}, } @misc{7928, author = {{Frahm, Björn}}, location = {{SeAMK, Seinäjoki, Finnland}}, title = {{{Scale-up of stirred vessels}}}, year = {{2019}}, } @misc{2391, author = {{Hernández Rodriguez, Tanja and Posch, Christoph and Schmutzhard, Julia and Stettner, Josef and Weihs, Claus and Pörtner, Ralf and Frahm, Björn}}, booktitle = {{Biotechnology and Bioengineering}}, issn = {{1097-0290}}, number = {{11}}, pages = {{2944--2959}}, publisher = {{Wiley}}, title = {{{Predicting industrial‐scale cell culture seed trains–A Bayesian framework for model fitting and parameter estimation, dealing with uncertainty in measurements and model parameters, applied to a nonlinear kinetic cell culture model, using an MCMC method}}}, doi = {{10.1002/bit.27125}}, volume = {{116}}, year = {{2019}}, } @misc{2400, author = {{Ifrim, George Adrian and Titica, Mariana and Deppe, Sahar and Frahm, Björn and Barbu, Marian and Caraman, Sergiu}}, booktitle = {{2019 23rd International Conference on System Theory, Control and Computing (ICSTCC)}}, isbn = {{9781728106991}}, issn = {{2372-1618}}, publisher = {{IEEE}}, title = {{{Multivariable control strategy for the photosynthetic cultures of microalgae}}}, doi = {{10.1109/icstcc.2019.8886109}}, year = {{2019}}, } @misc{2956, author = {{Möller, J. and Müller, J. and Hernández Rodriguez, Tanja and Kuchemüller, K. B. and Arndt, L. and Frahm, Björn and Eibl, R. and Eibl, D. and Pörtner, R.}}, location = {{Wädenswil, Switzerland}}, title = {{{Workflow for model-assisted design and scale-up of biopharmaceutical production processes}}}, year = {{2019}}, } @misc{2957, author = {{Möller, J. and Kuchemüller, K. B. and Moser, A. and Hass, V. C. and Hernández Rodriguez, Tanja and Deppe, S. and Frahm, Björn and Pörtner, R.}}, location = {{Florence, Italy}}, title = {{{Model-Assisted Design of Experiments}}}, year = {{2019}}, } @misc{2958, author = {{Ifrim, George Adrian and Titica, M. and Deppe, S. and Frahm, Björn and Barbu, M. and Caraman, S.}}, location = {{Sinaia, Romania}}, title = {{{Novel control strategy for microalgae in photobioreactor}}}, year = {{2019}}, } @misc{3000, author = {{Hernández Rodriguez, Tanja and Posch, C. and Schmutzhard, J. and Stettner, J. and Weihs, J. and Pörtner, R. and Frahm, Björn}}, location = {{Recklinghausen, Germany}}, title = {{{Predicting industrial scale cell culture seed trains – considerations of input uncertainty, new process data and prognostic intervals using a Bayesian approach and sequential Bayesian updating}}}, year = {{2019}}, } @misc{3001, author = {{Hernández Rodriguez, Tanja and Posch, C. and Schmutzhard, J. and Stettner, J. and Weihs, J. and Pörtner, R. and Frahm, Björn}}, location = {{Copenhagen, Denmark}}, title = {{{Predicting industrial scale cell culture seed trains – considerations of input uncertainty, new process data and prognostic intervals using a Bayesian approach and sequential Bayesian updating}}}, year = {{2019}}, } @misc{3002, author = {{Möller, J. and Kuchemüller, K. B. and Hernández Rodriguez, Tanja and Deppe, S. and Ifrim, George Adrian and Moser, A. and Hass, V. C. and Frahm, Björn and Pörtner, R.}}, location = {{Hamburg, Germany}}, title = {{{Model-Assisted Design of Experiments – Software Toolbox}}}, year = {{2019}}, } @misc{3003, author = {{Deppe, S. and Hernández Rodriguez, Tanja and Gassenmeier, Veronika and Tölle, M. and Kuhfuß, F. and Möller, J. and Kuchemüller, K. B. and Pörtner, R. and Moser, A. and Hass, V. C. and Ifrim, George Adrian and Frahm, Björn}}, location = {{Hamburg, Germany}}, title = {{{Model-assisted Design of Experiments for algae cultivation}}}, year = {{2019}}, } @misc{3004, author = {{Ifrim, George Adrian and Deppe, S. and Hernández Rodriguez, Tanja and Gassenmeier, Veronika and Frahm, Björn}}, location = {{Hamburg, Germany}}, title = {{{Modeling of microalgae in an air-lift photobioreactor for biomass production}}}, year = {{2019}}, } @misc{3005, author = {{Hernández Rodriguez, Tanja and Posch, C. and Schmutzhard, J. and Stettner, J. and Weihs, J. and Pörtner, R. and Frahm, Björn}}, location = {{Hamburg, Germany}}, title = {{{Predicting industrial scale cell culture seed trains – considerations of input uncertainty, new process data and prognostic intervals using a Bayesian approach and sequential Bayesian updating}}}, year = {{2019}}, } @misc{3006, author = {{Ifrim, George Adrian and Titica, M. and Deppe, S. and Frahm, Björn and Barbu, M. and Caraman, S.}}, location = {{Sinaia, Romania}}, title = {{{Multivariable control strategy for the photosynthetic cultures of microalgae}}}, year = {{2019}}, } @misc{7935, author = {{Hernández Rodriguez, Tanja and Frahm, Björn and Posch, Christoph and Schmutzhard, Julia and Stettner, Josef}}, location = {{Kundl, Austria}}, title = {{{A model-assisted approach for design, optimization and control of bioprocesses – a software tool for seed train simulation and optimization}}}, year = {{2018}}, } @misc{2390, author = {{Möller, J. and Kuchemüller, K. B. and Hernández Rodriguez, Tanja and Frahm, Björn and Hass, V. C. and Pörtner, R. }}, booktitle = {{American Pharmaceutical Review}}, issn = {{1099-8012}}, pages = {{39--41}}, publisher = {{Russel}}, title = {{{Model-Assisted Design of Process Strategies for Cell Culture Processes}}}, volume = {{3}}, year = {{2018}}, } @misc{2821, author = {{Hernández Rodriguez, Tanja and Krull, Susan and Hass, Volker C. and Möller, Johannes and Pörtner, Ralf and Frahm, Björn}}, booktitle = {{BMC Proceedings}}, issn = {{1753-6561}}, location = {{Lausanne, Switzerland}}, pages = {{P175}}, publisher = {{BioMed Central}}, title = {{{Model-assisted cell culture control – unstructured, unsegregated models as a key element for adaptive seed train and fed-batch optimization}}}, doi = {{10.1186/s12919-018-0097-x}}, volume = {{112}}, year = {{2018}}, } @misc{2955, author = {{Pörtner, R. and Möller, J. and Frahm, Björn and Hass, V. C.}}, location = {{Lisbon, Portugal}}, title = {{{Model-Assisted Design of Process Strategies for Cell Culture Processes}}}, year = {{2018}}, } @misc{2997, author = {{Möller, J. and Kuchemüller, K. B. and Freiberger, F. and Levermann, P. and Hernández Rodriguez, Tanja and Frahm, Björn and Hass, V. C. and Pörtner, R.}}, location = {{Recklinghausen, Germany}}, title = {{{Model-Assisted Design and Optimization of Process Strategies}}}, year = {{2018}}, } @misc{2999, author = {{Hernández Rodriguez, Tanja and Möller, J. and Kuchemüller, K. B. and Freiberger, F. and Levermann, P. and Hass, V. C. and Frahm, Björn and Pörtner, R.}}, location = {{Berlin, Germany}}, title = {{{Model-Assisted Strategies for Design, Optimization and Control of Bioprocesses}}}, year = {{2018}}, } @misc{2920, author = {{Hernández Rodriguez, Tanja and Kern, S. and Platas Barradas, O. and Pörtner, R. and Frahm, Björn}}, location = {{Lemgo, Germany}}, title = {{{Produktion von Biopharmazeutika – Ein MATLAB©-Tool zur Simulation und Optimierung von Zellvermehrungsverfahren}}}, year = {{2017}}, } @misc{2921, author = {{Pörtner, R. and Möller, J. and Hernández Rodriguez, Tanja and Frahm, Björn and Hass, V. C.}}, location = {{Neu-Ulm, Germany}}, title = {{{Model-assisted design and optimization of biotechnological processes}}}, year = {{2017}}, } @misc{2950, author = {{Hernández Rodriguez, Tanja and Koopmann, K. S. and Klaes, J. and Kern, S. and Platas Barradas, O. and Pörtner, R. and Frahm, Björn}}, location = {{Munic, Germany}}, title = {{{Produktion von Biopharmazeutika – Ein MATLAB©-Tool zur Simulation und Optimierung von Zellvermehrungsverfahren}}}, year = {{2017}}, } @misc{2994, author = {{Hernández Rodriguez, Tanja and Koopmann, K. S. and Pörtner, R. and Frahm, Björn}}, location = {{Recklinghausen, Germany}}, title = {{{Influence of parameter accuracies in cell culture seed train simulations}}}, year = {{2017}}, } @misc{2995, author = {{Hernández Rodriguez, Tanja and Krull, S. and Hass, V. C. and Möller, J. and Pörtner, R. and Frahm, Björn}}, location = {{Lausanne, Switzerland}}, title = {{{Model-based cell culture control – unstructured, unsegregated models as a key element for adaptive seed train and fed-batch optimization}}}, year = {{2017}}, } @misc{2996, author = {{Hernández Rodriguez, Tanja and Krull, S. and Hass, V. C. and Pörtner, R. and Frahm, Björn}}, location = {{Neu-Ulm, Germany}}, title = {{{Model-based cell culture control – unstructured, unsegregated models as a key element for adaptive seed train and fed-batch optimization}}}, year = {{2017}}, } @inbook{2395, author = {{Pörtner, R. and Platas Barradas, O. and Frahm, Björn and Hass, V.C.}}, booktitle = {{Current Developments in Biotechnology and Bioengineering: Bioprocesses, Bioreactors and Controls}}, isbn = {{978-0-444-63663-8}}, pages = {{463--493}}, publisher = {{Elsevier}}, title = {{{Advanced Process and Control Strategies for Bioreactors}}}, doi = {{10.1016/b978-0-444-63663-8.00016-1}}, year = {{2016}}, } @misc{2991, author = {{Beshay, U. and Feldt, Sebastian and Schwarze, B. and Wefing, P. and Hahne, T. and Moschinski, J. and Müller, C. and Büker, R. and Kramer, M. and Brod, H. and Frahm, Björn}}, location = {{Recklinghausen, Germany}}, title = {{{DMA Photobioreactor System – Cultivation at low shear stress and optional membrane aeration}}}, year = {{2016}}, } @misc{2992, author = {{Hernández Rodriguez, Tanja and Vörtler, S. and Kern, S. and Platas Barradas, O. and Pörtner, R. and Frahm, Björn}}, location = {{Recklinghausen, Germany}}, title = {{{A software tool for biopharmaceutical seed train design and optimization}}}, year = {{2016}}, } @misc{2993, author = {{Koopmann, K. S. and Hernández Rodriguez, Tanja and Vörtler, S. and Beshay, U. and Möller, J. and Pörtner, R. and Frahm, Björn}}, location = {{Koblenz, Germany}}, title = {{{Simulation of cell culture seed trains – investigation of the influence of parameter inaccuracies}}}, year = {{2016}}, } @misc{2389, author = {{Kern, Simon and Platas-Barradas, Oscar and Pörtner, Ralf and Frahm, Björn}}, booktitle = {{Cytotechnology}}, issn = {{1573-0778}}, number = {{4}}, pages = {{1019--1032}}, publisher = {{Springer}}, title = {{{Model-based strategy for cell culture seed train layout verified at lab scale}}}, doi = {{10.1007/s10616-015-9858-9}}, volume = {{68}}, year = {{2015}}, } @misc{2819, author = {{Hernández Rodriguez, Tanja and Pörtner, Ralf and Frahm, Björn}}, booktitle = {{BMC proceedings / BioMed Central}}, issn = {{1753-6561}}, publisher = {{BioMed Central}}, title = {{{Considerations for cell passaging in cell culture seed trains}}}, doi = {{10.1186/1753-6561-9-s9-p43}}, volume = {{9}}, year = {{2015}}, } @misc{2820, author = {{Kern, Simon and Platas Barradas, Oscar and Schaletzky, Martin and Sandig, Volker and Frahm, Björn and Pörtner, Ralf}}, booktitle = {{BMC proceedings / BioMed Central}}, issn = {{1753-6561}}, publisher = {{BioMed Central}}, title = {{{Model-based strategy for cell culture seed train layout verified at lab scale}}}, doi = {{10.1186/1753-6561-9-s9-p44}}, volume = {{9}}, year = {{2015}}, } @misc{2917, author = {{Frahm, Björn and Pörtner, R. and Kern, S. and Hernández Rodriguez, Tanja}}, location = {{Frankfurt am Main, Germany}}, title = {{{Seed train design and optimization for animal cell suspension culture}}}, year = {{2015}}, } @misc{2919, author = {{Frahm, Björn and Hernández Rodriguez, Tanja and Kern, S. and Koopmann, K. S. and Beshay, U. and Platas-Barradas, O. and Pörtner, R.}}, location = {{Magdeburg, Germany}}, title = {{{Seed train design and optimization for animal cell suspension culture}}}, year = {{2015}}, } @misc{2985, author = {{Hernández Rodriguez, Tanja and Pörtner, R. and Frahm, Björn}}, location = {{Hamburg, Germany}}, title = {{{Considerations for cell passaging in cell culture seed trains}}}, year = {{2015}}, } @misc{2986, author = {{Kern, S. and Platas, O. and Schaletzky, M. and Sandig, V. and Frahm, Björn and Pörtner, R.}}, location = {{Hamburg, Germany}}, title = {{{Model-based strategy for cell culture seed train layout verified at lab scale}}}, year = {{2015}}, } @misc{2987, author = {{Hernández Rodriguez, Tanja and Pörtner, R. and Frahm, Björn}}, location = {{Munic, Germany}}, title = {{{A software tool for biopharmaceutical seed train design and optimization}}}, year = {{2015}}, } @misc{2988, author = {{Hernández Rodriguez, Tanja and Pörtner, R. and Frahm, Björn}}, location = {{Barcelona, Spain}}, title = {{{Considerations for cell passaging in cell culture seed trains}}}, year = {{2015}}, } @misc{2990, author = {{Kern, S. and Platas, O. and Schaletzky, M. and Sandig, V. and Frahm, Björn and Pörtner, R.}}, location = {{Barcelona, Spain}}, title = {{{Model-based strategy for cell culture seed train layout verified at lab scale}}}, year = {{2015}}, } @misc{2388, author = {{Hahne, T. and Schwarze, B. and Kramer, M. and Frahm, Björn}}, booktitle = {{Journal of Algal Biomass Utilization}}, issn = {{2229-6905}}, number = {{2}}, pages = {{66--73}}, publisher = {{PHYCO SPECTRUM}}, title = {{{Disposable algae cultivation for high-value products using all around LED-illumination directly on the bags}}}, volume = {{5}}, year = {{2014}}, } @misc{2878, abstract = {{Ein Bioreaktor mit einem Disposable Bag, der einen von einer Wandung (1) begrenzten Reaktorraum (2) aufweist, ist als Photo-Bioreaktor ausgelegt, bei dem in unmittelbarer Nachbarschaft der Wandung (1) des Disposable Bags Lichtquellen (LED-Streifen 6) angeordnet sind. }}, author = {{Frahm, Björn and Meier, Uwe}}, pages = {{9}}, title = {{{Beleuchtung von disposable Bioreaktoren}}}, year = {{2014}}, } @misc{2984, author = {{Drews, F. and Drews, G. and Folz, C. and Platz, G. and Gassenmeier, Thomas and Kramer, M. and Hundeiker, C. and Schwarze, B. and Frahm, Björn}}, location = {{Köthen, Germany}}, title = {{{Herstellung von Paramylon mit Euglena gracilis im disposable Bag mit LED-Beleuchtung direkt auf dessen Oberfläche}}}, year = {{2014}}, } @misc{2817, author = {{Hernández Rodriguez, Tanja and Pörtner, Ralf and Frahm, Björn}}, booktitle = {{BMC proceedings / BioMed Central }}, issn = {{1753-6561}}, publisher = {{BioMed Central }}, title = {{{Seed train optimization for suspension cell culture}}}, doi = {{10.1186/1753-6561-7-s6-p9}}, volume = {{7}}, year = {{2013}}, } @misc{2818, author = {{Kern, Simon and Platas, Oscar and Schaletzky, Martin and Sandig, Volker and Frahm, Björn and Pörtner, Ralf}}, booktitle = {{BMC proceedings / BioMed Central }}, issn = {{1753-6561}}, publisher = {{BioMed Central}}, title = {{{Model-based design of the first steps of a seed train for cell culture processes}}}, doi = {{10.1186/1753-6561-7-s6-p11}}, volume = {{7}}, year = {{2013}}, } @misc{2980, author = {{Kern, S. and Platas, O. and Schaletzky, M. and Sandig, V. and Frahm, Björn and Pörtner, R.}}, location = {{Bad Wildungen, Germany}}, title = {{{Modellgestützte Auslegung der ersten Schritte eines Seed-Trains für Zellkulturprozesse}}}, year = {{2013}}, } @misc{2981, author = {{Kern, S. and Platas, O. and Schaletzky, M. and Sandig, V. and Frahm, Björn and Pörtner, R.}}, location = {{Lille, France}}, title = {{{Model-based design of the first steps of a seed train for cell culture processes}}}, year = {{2013}}, } @misc{2982, author = {{Hahne, T. and Schwarze, B. and Moschinski, J. and Kuttig, A. and Kramer, M. and Frahm, Björn}}, location = {{Hamburg, Germany}}, title = {{{Disposable Algenkultivierung für hochpreisige Produkte mittels LED-Rundumbeleuchtung direkt auf den Bags}}}, year = {{2013}}, } @misc{2983, author = {{Hernández Rodriguez, Tanja and Pörtner, R. and Frahm, Björn}}, location = {{Lille, France}}, title = {{{Seed train optimization for suspension cell culture}}}, year = {{2013}}, } @inbook{10214, abstract = {{For the production of biopharmaceuticals a seed train is required to generate an adequate number of cells for inoculation of the production bioreactor. This seed train is time- and cost-intensive but offers potential for optimization. A method and a protocol are described for the seed train mapping, directed modeling without major effort, and its optimization regarding selected optimization criteria such as optimal points in time for cell passaging. Furthermore, the method can also be applied for the set-up of a new seed train, for example for a new cell line. Although the chapter is directed towards suspension cell lines, the method is also generally applicable, e.g. for adherent cell lines.}}, author = {{Frahm, Björn}}, booktitle = {{Animal Cell Biotechnology - Methods and Protocols}}, editor = {{Pörtner, Ralf}}, isbn = {{978-1-62703-732-7}}, issn = {{1940-6029}}, keywords = {{Seed train, Optimization, Modeling, Prediction, Space-Time-Yield (STY), Systems approach, Bioinformatics, Computational biotechnology, Suspension, Production}}, pages = {{355–367}}, publisher = {{Humana Press}}, title = {{{Seed Train Optimization for Cell Culture}}}, doi = {{10.1007/978-1-62703-733-4_22}}, volume = {{1104}}, year = {{2013}}, } @misc{2816, author = {{Frahm, Björn and Brod, H.}}, booktitle = {{Proceedings of the 21st Annual Meeting of the European Society for Animal Cell Technology (ESACT), Dublin, Ireland, June 7-10, 2009}}, isbn = {{978-94-007-0883-9}}, issn = {{978-94-007-0884-6}}, location = {{ Dublin, Ireland}}, pages = {{355--359}}, publisher = {{Springer}}, title = {{{Improving Cell Culture Bioreactor Performance for Sensitive Cell Lines by Dynamic Membrane Aeration (DMA)}}}, doi = {{10.1007/978-94-007-0884-6_56}}, volume = {{vol. 5}}, year = {{2012}}, } @misc{2877, abstract = {{Die Erfindung betrifft einen Photobioreaktor mit Belichtung durch rotatorisch oszillierend bewegte Lichtquellen (Lichtleiter, LEDs) sowie optional kombiniert rotatorisch oszillierend bewegte Membranflächen zum Gastransport. Vorteile sind unter anderem ein im zeitlichen Mittel räumlich homogener Lichteintrag, welcher über Intensität und Oszillation an die Kultur und deren Dichte angepasst werden kann, sowie ein scherarmer Leistungseintrag und optional eine scherarme blasenfreie Be- und Entgasung. }}, author = {{Brod, Helmut and Frahm, Björn}}, pages = {{19}}, title = {{{Photobioreaktor mit rotatorisch oszillierenden Lichtquellen}}}, year = {{2012}}, } @misc{2918, author = {{Van Hecke, W. and Haltrich, D. and Frahm, Björn and Brod, H. and Ludwig, R.}}, booktitle = {{Achema 2012}}, location = {{Frankfurt am Main, Germany}}, publisher = {{Vogel Business Media}}, title = {{{Modelling and upscaling of a biocatalytic cascade oxidation in a dynamic membrane aeration reactor}}}, year = {{2012}}, } @misc{2973, author = {{Marzougui, R. and Pörtner, R. and Frahm, Björn}}, location = {{Freiburg, Germany}}, title = {{{Optimierung des Seed trains von Suspensions-Zellkulturen}}}, year = {{2012}}, } @misc{2350, author = {{Van Hecke, Wouter and Haltrich, Dietmar and Frahm, Björn and Brod, Helmut and Dewulf, Jo and Van Langenhove, Herman and Ludwig, Roland}}, booktitle = {{Journal of Molecular Catalysis B: Enzymatic}}, issn = {{1381-1177}}, number = {{2}}, pages = {{154--161}}, publisher = {{Elsevier}}, title = {{{A biocatalytic cascade reaction sensitive to the gas–liquid interface: Modeling and upscaling in a dynamic membrane aeration reactor}}}, doi = {{10.1016/j.molcatb.2010.10.004}}, volume = {{68}}, year = {{2011}}, } @misc{2876, abstract = {{Die Erfindung betrifft einen Begaser zum Eintrag eines Gases oder Gasgemisches in eine Flüssigkeit sowie ein Verfahren zur Begasung von Flüssigkeiten. Der erf?ndungsgemäße Begaser umfasst einen Hohlraum, einen Gaseinlass zum Einleiten eines Gases in den Hohlraum und zwei oder mehr Flächen, die formschlüssig aufeinander gepresst sind oder gepresst werden können, so dass ein durch den Gaseinlass in den Hohlraum gedrücktes Gas durch die zwischen den zusammengepressten Flächen auftretenden Spalten entweicht. }}, author = {{Brod, Helmut and Frahm, Björn and Jenne, Marc and Kauling, Jörg and Schmitt, Franz and Seletzky, Juri}}, pages = {{32}}, title = {{{Flüssigkeitsbegaser}}}, year = {{2011}}, } @misc{2972, author = {{Van Hecke, W. and Haltrich, D. and Frahm, Björn and Brod, H. and Ludwig, R.}}, location = {{Berlin, Germany}}, title = {{{Modelling and upscaling of a biocatalytic cascade oxidation in a dynamic membrane aeration reactor}}}, year = {{2011}}, } @misc{2815, author = {{Dercks, B. and Frahm, Björn and Grünewald, M. and Kenig, E. and Lautenschleger, A. and Gorak, A. and Schmidt, P. and Sudhoff, D. and Ressler, S. and Zecirovic, R.}}, booktitle = {{Proceedings 19th International Congress of Chemical and Process Engineering}}, isbn = {{978-80-02-02250-3}}, location = {{Prague, CZ}}, publisher = {{Czech Society of Chemical Engineering}}, title = {{{Intensified absorption and distillation devices for modular chemical production processes}}}, year = {{2010}}, } @misc{2873, abstract = {{Die Erfindung betrifft ein Verfahren zur Reduzierung von Ablagerungen bei der Kultivierung von Organismen, insbesondere von Zellkulturen, welche zur Agglomeration bzw. Anhaftung an den Bioreaktor und seine Elemente neigen, oder bei denen Zelldebris oder Substanzen leicht agglomerieren bzw. anhaften.}}, author = {{Brod, Helmut and Frahm, Björn and Kauling, Jörg}}, pages = {{26}}, title = {{{Verfahren zur Reduzierung von Ablagerungen bei der Kultivierung von Organismen}}}, year = {{2010}}, } @misc{2874, abstract = {{Die Erfindung betrifft einen Bioreaktor, die Verwendung des Bioreaktors zur Kultivierung von Mikroorganismen oder Zellkulturen sowie ein Verfahren zur Kultivierung von Mikroorganismen oder Zellkulturen. }}, author = {{Brod, Helmut and Frahm, Björn and Jenne, Marc and Kauling, Jörg}}, pages = {{27}}, title = {{{Bioreaktor}}}, year = {{2010}}, } @misc{2875, abstract = {{Gegenstand der Erfindung ist ein neuartiges Begasungssystem, das insbesondere aber nicht ausschließlich in der Biotechnologie zur Versorgung von Zellen oder Mikroorganismen mit Sauerstoff einsetzbar ist. Das Begasungssystem umfasst eine Blasensäule und einen Verteiler. In dem Gefäß befindet sich ferner ein flüssiges Medium, das mit Gas versorgt werden soll. Es wird ein Vektor als Transportmittel für das Gas eingesetzt. Das Gas wird in die Blasensäule eingetragen und hier von dem Vektor aufgenommen. Der Vektor wird in Tropfenform über den Verteiler auf die Flüssigkeitsoberfläche aufgetragen, sinkt in dem Medium nach unten und gibt einen Teil des aufgenommenen Gases an das Medium ab. Am Boden des Gefäßes befindet sich eine Sammelvorrichtung, in der die Vektortropfen koaleszieren und wieder in die Blasensäule gelangen. Gegenstand der Erfindung ist weiterhin ein Bioreaktor umfassend das neuartige Begasungssystem. Gegenstand der Erfindung ist ferner ein Verfahren zur Begasung eines flüssigen Mediums, vorzugsweise einer Zellen oder Mikroorganismen enthaltenden wässrigen Suspension. }}, author = {{Frahm, Björn and Kauling, Jörg and Pütz, Andre and Schindler, Markus}}, pages = {{35}}, title = {{{Begasungssystem}}}, year = {{2010}}, } @misc{2892, author = {{Frahm, Björn and Brod, Helmut}}, location = {{Boston, USA}}, title = {{{Cultivation of sensitive cell lines - Improving bioreactor performance by Dynamic Membrane Aeration}}}, year = {{2010}}, } @misc{2913, author = {{Dercks, B. and Frahm, Björn and Grünewald, M. and Kenig, E. and Lautenschleger, A. and Gorak, A. and Schmidt, P. and Sudhoff, D. and Ressler, S. and Zecirovic, R.}}, location = {{Prague, Czech Republic}}, title = {{{Intensified absorption and distillation devices for modular chemical production processes}}}, year = {{2010}}, } @misc{2349, author = {{Frahm, Björn and Brod, Helmut and Langer, Uwe}}, booktitle = {{Cytotechnology}}, issn = {{1573-0778}}, number = {{1}}, pages = {{17--30}}, publisher = {{Springer}}, title = {{{Improving bioreactor cultivation conditions for sensitive cell lines by dynamic membrane aeration}}}, doi = {{10.1007/s10616-009-9189-9}}, volume = {{59}}, year = {{2009}}, } @misc{2872, abstract = {{Die Erfindung betrifft eine Vorrichtung und ein Verfahren zur Rückhaltung und Rückführung von Zellen in einem kontinuierlich oder absatzweise durchströmten Gefäß. Ferner betrifft die Erfindung ein Verfahren zur Herstellung einer Vorrichtung, mit dem Zellen in einem kontinuierlich oder absatzweise durchströmten Gefäß zurückgehalten und zurückgeführt werden können. }}, author = {{Braun, Arndt and Brod, Helmut and Frahm, Björn and Jenne, Marc and Kauling, Jörg and Kirchner, Stephan}}, pages = {{35}}, title = {{{Verfahren und Vorrichtung zur Rückhaltung und Rückführung von Zellen}}}, year = {{2009}}, } @misc{2912, author = {{Frahm, Björn and Brod, H. and Langer, U.}}, location = {{Frankfurt am Main, Germany}}, title = {{{Improving cell culture bioreactor performance by Dynamic Membrane Aeration (DMA)}}}, year = {{2009}}, } @misc{2970, author = {{Frahm, Björn and Brod, H. and Langer, U.}}, location = {{Dublin, Ireland}}, title = {{{Improving cell culture bioreactor performance by Dynamic Membrane Aeration (DMA)}}}, year = {{2009}}, } @misc{2971, author = {{Van Hecke, W. and Van Langenhovve, H. and Frahm, Björn and Brod, H. and Dewulf, J. and Haltrich, D. and Ludwig, R.}}, location = {{Krakow, Poland}}, title = {{{Upscaling the biocatalytic conversion of lactose to lactobionic acid with the dynamic membrane aeration reactor}}}, year = {{2009}}, } @misc{2911, author = {{Brod, H. and Kauling, J. and Frahm, Björn and Jenne, M. and Langer, U. and Bödeker, B.}}, location = {{Leverkusen, Germany}}, title = {{{Pushing the Limits in High-Density Mammalian Cell Fermentation}}}, year = {{2008}}, } @misc{2968, author = {{Frahm, Björn and Brod, H. and Burnett, M. and Langer, U. and Bödeker, B.}}, location = {{Palladium, Cologne, Germany}}, title = {{{High cell density bioreactor cultivation by Dynamic Membrane Aeration (DMA)}}}, year = {{2008}}, } @misc{2969, author = {{Frahm, Björn and Brod, Helmut}}, location = {{Leverkusen, Germany}}, title = {{{High cell density bioreactor cultivation by Dynamic Membrane Aeration (DMA)}}}, year = {{2008}}, } @misc{2348, author = {{Frahm, Björn and Kirchner, S. and Kauling, J. and Brod, H. and Langer, U. and Bödeker, B.}}, booktitle = {{Chemie Ingenieur Technik}}, issn = {{0009-286X}}, number = {{7}}, pages = {{1052--1058}}, publisher = {{WILEY-VCH Verlag}}, title = {{{Dynamische Membranbegasung im Bioreaktor zur Intensivierung der Sauerstoffversorgung empfindlicher Zelllinien}}}, doi = {{10.1002/cite.200700070}}, volume = {{79}}, year = {{2007}}, } @misc{2814, author = {{Pörtner, Ralf and Frahm, Björn and Lane, Paul and Munack, Axel and Kühn, Kathrin and Hass, Volker C.}}, booktitle = {{Cell Technology for Cell Products}}, isbn = {{978-1-402-05475-4}}, location = {{Harrogate, UK}}, pages = {{497--501}}, publisher = {{Springer}}, title = {{{Optimisation of Time-space-yield for Hybridoma fed-batch Cultures with an Adaptive Olfo-controller}}}, doi = {{10.1007/978-1-4020-5476-1_84}}, volume = {{vol. 3}}, year = {{2007}}, } @misc{2870, abstract = {{The procedure for gassing of liquid for cell cultures, comprises exchanging of gas over immersed membrane surfaces like hoses, cylinders or modules, and controlling the gassing rate change of the gas concentration and/or pressure of the gas or gas mixture or gas component flowing into/out of the area within the membrane surface. The membrane surface represents any rotatingly oscillating movement in the liquid. The gassing rate, transfer efficiency, mixing time and/or shear stress are controlled by change of the movement like amplitude and the equivalent number of revolutions. The procedure for gassing of liquid for cell cultures, comprises exchanging of gas over immersed membrane surfaces like hoses, cylinders or modules, and controlling the gassing rate change of the gas concentration and/or pressure of the gas or gas mixture or gas component flowing into/out of the area within the membrane surface. The membrane surface represents any rotatingly oscillating movement in the liquid. The gassing rate, transfer efficiency, mixing time and/or shear stress are controlled by change of the movement like amplitude, the equivalent number of revolutions, acceleration of the membrane surface, the delay of the membrane surface, the interruption of the movement or discontinuity. The course of motion is not restricted to recurring samples. The material transfer is increased by mounting of immovable current interfering elements. The disturb of the current forms by the rotatingly oscillating movement of the membrane surfaces. The supply of the membrane surface is undertaken with the help of flexible hoses or turning seals for the supply and discharge of gas. The membrane surface is used for the production of micro-bubbles or gas bubbles in the liquid. Rotor arms rotate in one of the rotation directions curved around the drive shaft. An independent claim is included for a device for gassing of liquid for cell cultures. }}, author = {{Brod, Helmut and Frahm, Björn and Kauling, Jörg and Rose, Reinhold}}, title = {{{Procedure for gassing of liquid for cell cultures, comprises exchanging of gas over immersed membrane surfaces and controlling the gassing rate change of the gas concentration and/or pressure of the gas or gas mixture or gas component}}}, year = {{2007}}, } @misc{2871, abstract = {{Gegenstand der Erfindung ist ein um seine ortsfeste, bevorzugt vertikale Achse oszillatorischrotierend angetriebener Reaktor für bevorzugt biotechnologische und pharmazeutische Anwendungen. Mit seinen prozessintensivierenden Eigenschaften für das Mischen, das Suspendieren, den Gasstofftransport, die Wärmeübertragung, die Bestrahlung und die Partikelrückhaltung wird die Anwendbarkeit im großtechnischen Maßstab gewährleistet. Der ohne Wellenabdichtung auskommende Reaktor erlaubt eine steriltechnisch besonders robuste Produktion unter Verzicht auf eine Reinigung und Reinigungsvalidierung erfordert, wenn der Reaktor als Einwegreaktor ausgeführt ist. }}, author = {{Brod, Helmut and Frahm, Björn and Kauling, Jörg and Poggel, Martin and Rose, Reinhold and Schmidt, Sebastian }}, pages = {{56}}, title = {{{Verfahren und Vorrichtung zur Be- und Entgasung von Flüssigkeiten, insbesondere in der Biotechnologie und speziell von Zellkulturen}}}, year = {{2007}}, } @misc{2909, author = {{Brod, Helmut and Frahm, Björn and Kauling, Jörg}}, location = {{Würzburg, Germany}}, title = {{{Die dynamische Membranbegasung – ein Ansatz zur Intensivierung der Sauerstoffversorgung tierischer Zellkulturen}}}, year = {{2007}}, } @misc{2910, author = {{Brod, Helmut and Frahm, Björn and Kauling, Jörg}}, location = {{Osnabrück, Germany}}, title = {{{Die dynamische Membranbegasung – ein Ansatz zur Intensivierung der Sauerstoffversorgung tierischer Zellkulturen}}}, year = {{2007}}, } @misc{2967, author = {{Frahm, Björn and Kirchner, S. and Rose, R. and Jenne, M. and Kauling, J. and Brod, H. and Jöris, K. and Wischniewski, M. and Langer, U. and Bödeker, B.}}, location = {{Leverkusen, Germany}}, title = {{{High cell density bioreactor cultivation by Dynamic Membrane Aeration (DMA)}}}, year = {{2007}}, } @misc{2347, author = {{Frahm, Björn and Lane, Paul and Munack, Axel and Pörtner, Ralf}}, booktitle = {{Chemie Ingenieur Technik}}, issn = {{1522-2640}}, number = {{4}}, pages = {{429--435}}, publisher = {{WILEY-VCH Verlag}}, title = {{{Optimierung und Steuerung von Zellkultur-Fed-Batch-Prozessen mittels einer Kollokationsmethode}}}, doi = {{10.1002/cite.200407094}}, volume = {{77}}, year = {{2005}}, } @misc{2813, author = {{Frahm, Björn and Pörtner, R.}}, booktitle = {{Animal Cell Technology Meets Genomics}}, isbn = {{1-4020-2791-5}}, location = {{Granada}}, pages = {{693--695}}, publisher = {{Springer}}, title = {{{Flexible Fed-Batch Process Control of Animal Cells}}}, doi = {{10.1007/1-4020-3103-3_142}}, volume = {{vol. 2}}, year = {{2005}}, } @misc{2907, author = {{Pörtner, Ralf and Frahm, Björn and Lane, P. and Munack, A.}}, location = {{Harrogate, UK}}, title = {{{Optimisation of time-space-yield for hybridoma fed-batch cultures with an adaptive OLFO-controller}}}, year = {{2005}}, } @misc{2908, author = {{Pörtner, R. and Frahm, Björn and Hass, V. C. and Lane, P. and Munack, A.}}, location = {{Wiesbaden, Germany}}, title = {{{Optimierung und Steuerung von Zellkultur-Fed-Batch-Prozessen mittels einer Kollokationsmethode}}}, year = {{2005}}, } @misc{2345, author = {{Pörtner, Ralf and Schwabe, Jan-Oliver and Frahm, Björn}}, booktitle = {{Biotechnology and Applied Biochemistry}}, issn = {{1470-8744}}, publisher = {{Wiley-Blackwell}}, title = {{{Evaluation of selected control strategies for fed-batch cultures of a hybridoma cell line}}}, doi = {{10.1042/ba20030168}}, volume = {{40}}, year = {{2004}}, } @misc{7934, author = {{Frahm, Björn and Pörtner, Ralf}}, location = {{Manchester, UK}}, title = {{{Fed-batch-cultivation of animal cells: Model-based, adaptive control in comparison to alternative control strategies}}}, year = {{2003}}, } @misc{2343, author = {{Frahm, Björn and Hass, V. C. and Lane, P. and Munack, A. and Märkl, H. and Pörtner, R.}}, booktitle = {{Chemie Ingenieur Technik}}, issn = {{1522-2640}}, number = {{4}}, pages = {{457--460}}, publisher = {{WILEY-VCH Verlag}}, title = {{{Fed-Batch-Kultivierung tierischer Zellen - Eine Herausforderung zur adaptiven, modellbasierten Steuerung}}}, doi = {{10.1002/cite.200390093}}, volume = {{75}}, year = {{2003}}, } @misc{2344, author = {{Frahm, Björn and Lane, P. and Märkl, H. and Pörtner, R.}}, booktitle = {{Bioprocess and Biosystems Engineering}}, issn = {{1615-7591}}, number = {{1}}, pages = {{1--10}}, publisher = {{Springer}}, title = {{{Improvement of a mammalian cell culture process by adaptive, model-based dialysis fed-batch cultivation and suppression of apoptosis}}}, doi = {{10.1007/s00449-003-0335-z}}, volume = {{26}}, year = {{2003}}, } @phdthesis{2393, abstract = {{Die wirtschaftlich immer mehr an Bedeutung gewinnende Kultivierung tierischer Zelllinien umfasst zahlreiche Anwendungen in der Pharmaherstellung und Medizintechnik. Eine Vielzahl der Produkte (Diagnostika, Impfstoffe, Therapeutika) wird in Fed-Batch-Prozessen hergestellt. Für die verbesserte Steuerung von derartigen Fed-Batch-Prozessen stellt der Autor eine adaptive, modellgestützte Steuerung vor. Anwendungsbeispiele veranschaulichen das Potential und die Flexibilität der Steuerung und ihre Universalität bezüglich verschiedener Kultivierungssysteme und Zelllinien. Da auch die gelöst-CO2-Konzentration und die Atmungsaktivität der Zellen zunehmend Bedeutung in der Prozessführung erlangen, stellt dieses Buch weiterhin die entwickelte Erfassung dieser Größen per Abgasanalytik und Modellierung des Kohlendioxidtransfers vor.}}, author = {{Frahm, Björn}}, isbn = {{ 978-3-8334-0111-4 }}, keywords = {{Tierzelle, Suspensionskultur, Prozesssteuerung}}, pages = {{120}}, publisher = {{Books on Demand GmbH}}, title = {{{Adaptive, modellgestützte Prozessführung von Suspensionskulturen tierischer Zellen}}}, year = {{2003}}, } @misc{2435, author = {{Frahm, Björn and Müller-Landré, B. and Wiggers de Almeida, G. and Singer, M. and Rausch, M. and Lane, P. and Munack, A. and Hass, V. C. and Pörtner, R.}}, booktitle = {{Technische Systeme für Biotechnologie und Umwelt}}, editor = {{Beckmann, Dieter}}, isbn = {{3-00-011287-1}}, location = {{Heilbad Heiligenstadt}}, pages = {{503--509}}, publisher = {{Inst. für Bioprozess- und Analysenmesstechnik }}, title = {{{Fed-batch cultivation of animal cells - a challenge for adaptive, model-based control}}}, year = {{2003}}, } @misc{2436, author = {{Kühn, K. and Frahm, Björn and Pörtner, R. and Lane, P. and Munack, A. and Hass, V. C.}}, booktitle = {{ ECCE - 4th European Congress of Chemical Engineering}}, isbn = {{84-88233-35-3}}, location = {{Granada}}, publisher = {{ECCE4}}, title = {{{Adaptive, Model-based Control by the Open-Loop-Feedback-Optimal (OLFO) Controller for the Cultivation of Hybridoma Cells}}}, volume = {{10}}, year = {{2003}}, } @misc{2902, author = {{Frahm, Björn and Pörtner, Ralf}}, location = {{Göttingen, Germany}}, title = {{{Fed-Batch-Kultivierungen tierischer Zellen – eine Herausforderung an eine modellgestützte, adaptive Steuerung}}}, year = {{2003}}, } @misc{2903, author = {{Hass, V. C. and Kühn, K. and Frahm, Björn and Pörtner, R. and Lane, P. and Munack, A.}}, location = {{München}}, title = {{{Ein strukturiertes Kompartiment-Modell zur Beschreibung der Kultivierung von Hybridomazellen als Teil einer adaptiven, modellgestützten Prozessführung}}}, year = {{2003}}, } @misc{2905, author = {{Frahm, Björn and Lane, P. and Munack, A. and Hass, V. C. and Pörtner, Ralf}}, location = {{Frankfurt am Main, Germany}}, title = {{{Fed-batch-cultivation of animal cells: Model-based, adaptive control in comparison to alternative control strategies}}}, year = {{2003}}, } @misc{2906, author = {{Pörtner, Ralf and Frahm, Björn and Lane, P. and Hass, V. C. and Munack, A. and Märkl, H.}}, location = {{Bad Dürkheim, Germany}}, title = {{{Fed-Batch-Kultivierung tierischer Zellen – eine Herausforderung für eine adaptive, modellgestützte Steuerung}}}, year = {{2003}}, } @misc{2964, author = {{Frahm, Björn and Pörtner, Ralf}}, location = {{Manchester, UK}}, title = {{{CO2-off-gas measurement for animal cell culture processes}}}, year = {{2003}}, } @misc{2965, author = {{Frahm, Björn and Pörtner, Ralf}}, location = {{Granada, Spain}}, title = {{{Flexible fed-batch process control of animal cells}}}, year = {{2003}}, } @misc{2966, author = {{Kühn, K. and Frahm, Björn and Pörtner, Ralf and Lane, P. and Munack, A. and Hass, V. C.}}, location = {{Granada, Spain}}, title = {{{Adaptive, Model-based Control by the Open-Loop-Feedback-Optimal (OLFO) Controller for the Cultivation of Hybridoma Cells}}}, year = {{2003}}, } @misc{2340, author = {{Frahm, Björn and Blank, H.-C. and Cornand, P. and Oelßner, W. and Guth, U. and Lane, P. and Munack, A. and Johannsen, K. and Pörtner, R.}}, booktitle = {{Journal of Biotechnology}}, issn = {{1873-4863 }}, keywords = {{Dissolved carbon dioxide, Carbon dioxide production rate, Carbon dioxide transfer rate, Off-gas measurement, Mammalian cell suspension culture}}, number = {{2}}, pages = {{133--148}}, publisher = {{Elsevier}}, title = {{{Determination of dissolved CO2 concentration and CO2 production rate of mammalian cell suspension culture based on off-gas measurement}}}, doi = {{https://doi.org/10.1016/S0168-1656(02)00180-3}}, volume = {{99}}, year = {{2002}}, } @misc{2341, author = {{Frahm, Björn and Lane, P. and Atzert, H. and Munack, A. and Hoffmann, M. and Hass, V. C. and Pörtner, R.}}, booktitle = {{Biotechnology Progress}}, issn = {{1520-6033}}, number = {{5}}, pages = {{1095--1103}}, publisher = {{ Wiley }}, title = {{{Adaptive, Model-Based Control by the Open-Loop-Feedback-Optimal (OLFO) Controller for the Effective Fed-Batch Cultivation of Hybridoma Cells}}}, doi = {{10.1021/bp020035y}}, volume = {{18}}, year = {{2002}}, } @misc{2342, author = {{Frahm, Björn and Pörtner, R.}}, booktitle = {{BIOforum}}, issn = {{0940-0079}}, pages = {{179--180}}, publisher = {{GIT-Verlag}}, title = {{{Reaktor-Abgasmessungen bei Zellkulturen}}}, volume = {{4}}, year = {{2002}}, } @misc{2431, author = {{Frahm, Björn and Pörtner, Ralf}}, booktitle = {{Biosystemtechnik: Innovative Biosystemtechnik - Sensorik, Aktorik und Auswertung biotechnologischer Prozesse}}, editor = {{Kaden , Heiner }}, isbn = {{3-00-009026-6}}, location = {{Waldheim/Sa. }}, pages = {{39--48}}, publisher = {{Kurt-Schwabe-Inst. }}, title = {{{Messung und Simulation des Kohlendioxidausstoßes von Zellkulturprozessen}}}, year = {{2002}}, } @misc{2897, author = {{Frahm, Björn and Pörtner, Ralf}}, location = {{Wiesbaden, Germany}}, title = {{{Messung und Simulation des Kohlendioxidausstoßes von Zellkulturprozessen}}}, year = {{2002}}, } @misc{2898, author = {{Frahm, Björn and Pörtner, Ralf}}, location = {{Lonza Biologics, Slough, UK}}, title = {{{Adaptive, model-based control by the OLFO-controller for the fed-batch cultivation of animal cells}}}, year = {{2002}}, } @misc{2899, author = {{Frahm, Björn and Pörtner, Ralf}}, location = {{Birmingham, UK}}, title = {{{Adaptive, model-based control by the OLFO-controller for the fed-batch cultivation of animal cells}}}, year = {{2002}}, } @misc{2900, author = {{Frahm, Björn and Müller-Landré, B. and Wiggers de Almeida, G. and Singer, M. and Rausch, M. and Lane, P. and Munack, A. and Hass, V. C. and Pörtner, R.}}, location = {{Heilbad Heiligenstadt, Germany}}, title = {{{Fed-batch cultivation of animal cells - a challenge for adaptive, model-based control}}}, year = {{2002}}, } @misc{7933, author = {{Frahm, Björn and Pörtner, Ralf}}, location = {{Waldheim, Germany}}, title = {{{Messung und Simulation des Kohlendioxidausstoßes von Zellkulturprozessen}}}, year = {{2001}}, } @misc{2427, author = {{Frahm, Björn and Atzert, H. and Lane, P. and Hoffmann, M. and Hass, V. C. and Munack, A. and Pörtner, Ralf}}, booktitle = {{Animal Cell Technology: From Target to Market}}, isbn = {{9789401038973}}, pages = {{446--448}}, publisher = {{Springer}}, title = {{{Development of an Automated, Adaptive Model-Based Control for the Effective Cultivation of Hybridoma Cells}}}, doi = {{10.1007/978-94-010-0369-8_107}}, volume = {{vol. 1}}, year = {{2001}}, } @misc{2429, author = {{Hass, V. C. and Lane, P. and Hoffmann, M. and Frahm, Björn and Schwabe, J.-O. and Pörtner, R. and Munack, A.}}, location = {{Québec City, Québec, Canada}}, title = {{{Model-Based Control of Hybridoma Cell Cultures}}}, year = {{2001}}, } @misc{2894, author = {{Hoffmann, M. and Hass, V. C. and Frahm, Björn and Schwabe, J.-O. and Pörtner, R. and Lane, P. and Munack, A.}}, location = {{Leipzig, Germany}}, title = {{{Untersuchung verschiedener mathematischer Modelle in Hinblick auf ihre Eignung für die adaptive Prozessführung von Hybridoma Zellkulturen}}}, year = {{2001}}, } @misc{2895, author = {{Frahm, Björn and Pörtner, R.}}, location = {{Hannover}}, title = {{{Arbeitsschwerpunkte TUHH, Bioprozess- und Bioverfahrenstechnik, Arbeitsgruppe Zellkulturtechnik}}}, year = {{2001}}, } @misc{2960, author = {{Frahm, Björn and Atzert, H. and Schwabe, J.-O. and Lane, P. and Munack, A. and Hoffmann, M. and Hass, V. C. and Pörtner, R.}}, location = {{Leipzig, Germany}}, title = {{{Adaptive modellgestützte Steuerung von Zellkulturprozessen}}}, year = {{2001}}, } @misc{2961, author = {{Lane, P. and Frahm, Björn and Atzert, H. and Schwabe, J.-O. and Hoffmann, M. and Hass, V. C. and Pörtner, R.}}, location = {{Leipzig, Germany}}, title = {{{Design of Feeding Strategies for Fed-Batch Cultures of Animal Cells by the Method of Inequalities}}}, year = {{2001}}, } @misc{2962, author = {{Frahm, Björn and Atzert, H. and Lane, P. and Hoffmann, M. and Hass, V. C. and Munack, A. and Pörtner, R.}}, location = {{Tylösand, Sweden}}, title = {{{Development of an automated, model-based, adaptive control for the effective cultivation of hybridoma cells}}}, year = {{2001}}, } @misc{2963, author = {{Hass, V.C. and Lane, P. and Hoffmann, M. and Frahm, Björn and Schwabe, J.-O. and Pörtner, R. and Munack, A.}}, booktitle = {{Computer Applications in Biotechnology, 2001: Modelling, Monitoring and Control of Biotechnological Processes}}, isbn = {{ 0080436811 }}, issn = {{ 1474-6670 }}, location = {{Québec City, Québec, Canada}}, pages = {{323--329}}, publisher = {{ScienceDirect}}, title = {{{Model-Based Control of Hybridoma Cell Cultures}}}, doi = {{https://doi.org/10.1016/S1474-6670(17)34240-4}}, volume = {{34}}, year = {{2001}}, } @misc{2893, author = {{Anderelei, T. and Frahm, Björn and Büchs, J.}}, location = {{Bamberg, Germany}}, title = {{{Online-Bestimmung der Sauerstofftransferrate (OTR) und der Kohlendioxidtransferrate (CTR) in geschüttelten Bioreaktoren}}}, year = {{2000}}, } @misc{2959, author = {{Hoffmann, M. and Frahm, Björn and Schwabe, J.-O. and Lane, P. and Pörtner, R. and Hass, V. C. and Munack, A.}}, location = {{Heilbad Heiligenstadt, Germany}}, title = {{{Modellgestützte Prozessführung für Hybridoma-Kulturen mit Hilfe des Open-Loop-Feedback-Optimal (OLFO)- Algorithmus}}}, year = {{2000}}, }