Former Employees

Former Administrative Staff
  • Jeanette Felsberg

  • Cornelia Heinz

  • Jutta Hülsmann

  • Alexandra Kalski

  • Madeleine Otto

  • Heike Wessling

Former Post Doctorates

Former Doctoral Researchers

Vincent Bernemann

Vincent Bernemann, M.Sc.


Eißendorfer Str. 38

Building O, Room 1.015

21073 Hamburg

Phone +49 40 42878 - 2603

Mail Vincent Bernemann


Biography

Vincent Bernemann completed his apprenticeship as a plant mechanic at Evonik Industries AG from 2011 to 2015. At the same time, he completed a degree in Industrial Service Management at the University of Applied Sciences Dortmund.

From 2015, he deepened his training by studying process engineering at the Technical University of Hamburg, initially in the bachelor's program and from 2019 in the master's program. Since graduating in 2021, he is employed as a research assistant at the Institute for Multiphase Flows.

Research

As part of the multiphase bioreactor research group, Vincent Bernemann investigates single-use bioreactors in various scales from 250 mL to 2000 L. In collaboration with Sartorius Stedim GmbH, the reactors are characterized and optimized experimentally with respect to various process parameters such as mass transfer, bubble size distribution, energy input and mixing time.

Education
  • Fundamentals of Material Engineering

Publications

[189724]
Title: Advances in Characterization of Industrial Bioreactors for Cell Culture Process. <em>Biopharmaceutical Manufacturing</em>
Written by: Fitschen, J.; Hofmann, S.; Kursula, L.; Haase, I.; Wucherpfennig, T.; Schlüter, M.
in: <em>Biopharmaceutical Manufacturing</em>. (2024).
Volume: Number:
on pages:
Chapter: 3
Editor: In Pörtner, Ralf (Eds.)
Publisher: Springer International Publishing:
Series:
Address:
Edition:
ISBN: 978-3-031-45668-8
how published:
Organization:
School:
Institution:
Type:
DOI: 10.1007/978-3-031-45669-5
URL:
ARXIVID:
PMID:

Note:

Abstract: Aerated stirred tank reactors are widely used in the biopharmaceutical industry for cell culture applications due to their flexibility and broad range of uses. This book chapter provides an overview of the main characterization methods for aerated stirred tank reactors in the context of cell culture processes. The methods described include mechanical power input, volumetric mass transfer, flow field, and mixing characterization. Examples are given using stirred tank reactors of different scales, ranging from a 3 L laboratory scale to a 15,000 L industrial scale. The chapter also discusses recent developments in the use of mobile, encapsulated sensors known as Lagrangian Sensor Particles (LSP) for continuous data collection and transmission throughout the entire reactor volume, providing insights from the perspective of cells during a cell culture process. Additionally, the state-of-the-art in numerical flow simulation is discussed, using aerated stirred tank reactors as an example to illustrate the challenges and opportunities offered by numerical flow simulation. It is highlighted that the methods described are specifically focused on cell culture applications, which have lower specific power inputs and aeration rates compared to other types of applications such as microbial fermentations or chemical reactions. The chapter also provides a brief overview of the fundamentals of aerated stirred tank reactors, including their design and components, and emphasizes the importance of equipment characterization for successful process transfer and scaleup in cell culture processes.

Daniel Bezecny

Dipl.-Phys. Daniel Bezecny

2012 - 2019        Research Fellow at the IMS

Research Expertise


Melanie Bothe

Dipl.-Ing. Melanie Bothe

2011 - 2014        Research Fellow at the IMS

Research Expertise

  • Experimental analysis of local mass transfer phenomena in bubble columns using optical measurement techniques

  • Validation of simulations based on Direct Numerical Simulation (DNS) and Computer Fluid Dynamics (CFD)


Christian Busch

Christian Busch, M.Sc.

2017 - 2018        Research Fellow at the IMS

Research Expertise

  • Liquid/liquid and liquid/gas jet-loop-reactors

  • Liquid/gas trickle-bed-reactors

  • Characterization of a jet stream via Particle Imaging Velocimetry (PIV)


Raffaele Colombi

Raffaele Colombi, M.Sc.

2018 - 2022        Research Fellow at the IMS

Research Expertise


Jürgen Fitschen

Dr.-Ing. Jürgen Fitschen

2018 - 2023        Research Fellow at the IMS

Boehringer Ingelheim Pharma GmbH & Co. KG
Bioprocess Development Biologicals

Binger Strasse 173

55216 Ingelheim am Rhein

Phone +49 7351 54-177970

Mail Dr. Jürgen Fitschen

Research Expertise

  • Large Scale Bioreactors

  • Characterization of Heterogeneities in Aerated Stirred Tank Reactors

  • Characterization of Mixing Time


Tobias Freund

Tobias Freund, M.Sc.

2021 - 2022        Research Fellow at the IMS

Research Expertise

CFD Simulation of non-Newtonian fluids


Torben Frey

Torben Frey, M.Sc.

2019 - 2023        Research Fellow at the IMS

Research Expertise

Simulation and Modeling of Static Mixers within the framework of KoPPonA 2.0


Research

Continuous Polymerization in Modular, Intelligent Reactors Resistant to the Formation of Deposits (KoPPonA 2.0)

The main objective of the ENPRO 2.0 initiative is to increase energy efficiency of new production processes. A number of energy demanding and inefficient processes are allocated within the German chemical industry, especially the production of pharmaceutical, fine and special chemicals. The concerned products are mostly produced utilizing multi-product plants and small batch processes due to small throughput. During the first phase of the ENPRO 1.0 initiative (2014-2017) the project partners have developed flexible, scalable and modular plant concepts. Micro-structured devices have been proven to suit requirements for the combined product and process development. However, one drawback of micro-structured mixers, reactors and heat exchangers for continuous processes is the formation of gel or solid particles leading to fouling and blocking of the device.

The KoPPonA 2.0 project drives the development of continuous process concepts for polymer production which are sensitive to fouling. A conglomerate of plant operators, equipment and sensor suppliers, material scientists and process engineers work together in KoPPonA 2.0 to research causes and preventive measures of fouling. KoPPonA 2.0 uses innovative approaches in plant design, surface modification, and reaction control are used to allow efficient and safe operation of continuous polymerization processes. By investigating basic fouling mechanisms in continuous polymerization processes a universal comprehension of fouling is to be derived.

The Institute of Multiphase Flows (V-5) generates a comprehensive computational fluid dynamics (CFD) model of the process components that are prone to fouling. The model incorporates hydrodynamic flow phenomena, mass transfer, kinetics and different fouling mechanisms. The models are validated by means of Confocal Laser Scanning Microscopy (CLSM) to visualize three-dimensional concentration distribution at micro scale (resolution down to 1 μm) with Laser-Induced Fluorescence (LIF). Furthermore, reactive models are validated by means of the novel imaging UV/Vis spectroscopy developed at the IMS.

Education

Graduate Teaching Assistant

  • Process Design Course WiSe 19/20

  • Computional Fluid Dynamics in Process Engineering SoSe 20, SoSe 21, SoSe 22, and SoSe 23

  • Lagrangian Transport in Turbulent Flows SoSe 20 and SoSe 21

  • Turbulent Flows SoSe 22 and SoSe 23

Supervised Theses

  • "Education 4.0: Development of an Extended Reality Tool for CFD-aided Design and Development of a Shell-Tube Heat Exchanger (working title)", Jeswin Kannampuzha Francis, Master thesis, ongoing

  • "Experimentelle Bestimmung der Löslichkeit von Stickstoffmonixid in Methanol mithilfe einer chemischen Reaktion", Xuan My Le, Project thesis, 2023

  • "Experimentelle Untersuchung der laminaren Mikrovermischung in einem Kaskadenmischer durch konfokale LIF-Messung einer reaktiven Strömung", Anna-Christin Menzel, Master thesis, 2023

  • "Analysis of Transport Barriers in Continuous Mixers by means of Lagrangian Coherent Structures", Christoph Wigger, Master thesis, 2023

  • "Experimenteller Vergleich der bildgebenden und globalen UV/Vis-Spektroskopie zur Charakterisierung der Mikromischung in einem Kaskadenmischer", Xuan My Le, Master thesis, 2023

  • "Comparison of the Lattice-Boltzmann Method and Finite Volume Method in continuously operated static mixers - a CFD benchmark study", Roman Neubauer, Master thesis, 2023

  • "Erstellung einer 1D- und 3D-CFD Methodik zur Berechnung und Optimierung einer neuen innovativen Wärmetauscher-Technologie im Motorsport", Hendrik Doß, Master thesis, 2022

  • "Experimentelle Untersuchung des Mischverhaltens in einem Milli-Kaskadenmischer bei kleinen Reynoldszahlen mit Hilfe der konfokalen Laserscanning-Mikroskopie", Sabrina Bauschmann, Bachelor thesis, 2022

  • "Effect of a Chemical Reaction on Grid Convergence of a Direct Numerical Simulation", Chandrahas Rao Sampelli, Project thesis, 2022

  • "Experimental Investigations of Mixing in a Split and Recombine Mixer using Confocal Laser Scanning Microscopy", Nithin Thonakkara James, Project Work, 2021

  • "Numerische Simulation der Mischleistung in einem strukturierten Rohrreaktor bei einem hohen Viskositätsverhältnis der Teilströme", Vincent Bernemann, Master thesis, 2021

  • "Experimentelle Untersuchung der Übertragbarkeit eines Mischprozesses vom Labordissolver auf eine duale asymmetrische Zentrifuge bei wässrigen Lacksystemen", Gerrit Spiller, Master thesis, 2021

  • „Numerische Simulation einer parallel-kompetitiven chemischen Reaktion mit steifem Differentialgleichungssystem in einem mikro-strukturierten Strömungskanal bei kleinen Reynoldszahlen", Tobias Freund, Master thesis, 2021

  • "Comparison of Active and Passive Micro Mixers Designed for Asymmetric Mixing Tasks", Kayla Reata Dittmer, Bachelor thesis, 2020

  • "Experimental Analysis of the Mixing Performance in Micro Channels at High Volume Flow Ratios and Low Reynolds Numbers", Rieke Schlütemann, Bachelor thesis, 2020

Oral and Poster Presentation

Lectures

  • Frey, T., Hoffmann, M., Schlüter, M.: "Experimental and CFD Study on Local Selectivity Distributions in a Stiff Reactive System", 14th ECCE and 7th ECAB, Berlin, 2023, lecture.

  • Frey, T., Grabellus, M., Le, X. M., Hoffmann, M., Herbstritt, F., Grünewald, M., Schlüter, M.: "Local interpretation of micro mixing through the Villermaux-Dushman reaction and the imaging UV-Vis spectroscopy", 17th European Conference on Mixing, Porto, 2023, lecture.

  • Schwarz, S.; Grünewald, M.; Biessey, P.; Frey, T.; Schlüter, M.; Hoffmann, M.: "CFD-based compartment modeling approach for continuous polymer reactors by means of the Mean-Age theory". (Bio)Process Engineering - a Key to Sustainable Development, joint event of ProcessNet, DECHEMA-BioTechNet Jahrestagungen 2022, 13th ESBES Symposium, Aachen, 2022, lecture.

  • Frey, T.; Hoffmann, M.; Schlüter, M.: "Visualizing Reactive Mixing Phenomena with the Novel Imaging UV/Vis Spectroscopy in Asymmetric and Transient Flows". (Bio)Process Engineering - a Key to Sustainable Development, joint event of ProcessNet, DECHEMA-BioTechNet Jahrestagungen 2022, 13th ESBES Symposium, Aachen, 2022, lecture.

  • Frey, T.; Hoffmann, M.; Schlüter, M.: "Visualizing Reactive Mixing Phenomena in Milli and Micro Channels". NAMF Mixing XXVII, virtual, 2022, lecture.

  • Frey, T.; Schwarz, S.; Biessey, P.; Hoffmann, M.; Grünewald, M; Schlüter, M.: "Modeling Polymer Fouling with an Euler-Lagrangian Approach in a Milli-Reactor with Static Mixing Elements". 13th ECCE, virtual, 2021, lecture.

Poster Presentations

  • Frey, T.; Schwarz, S.; Hoffmann, M.; Grünewald, M.; Schlüter, M.: "CFD unterstützte Auslegung und Compartment modellierung eines kontinuierlich betriebenen Reaktorsystems für Polymerisationsreaktionen". Jahrestreffen der ProcessNet-Fachgemeinschaft "Prozess-, Apparate- und Anlagentechnik", Frankfurt a. M., 2022, poster presentation.

  • Schwarz, S.; Frey, T.; Hoffmann, M.; Biessey, P.; Schlüter, M.; Grünewald, M: "CFD-based compartment modeling of static mixing elements for continuous polymer reactors by means of the Mean-Age theory". Annual Meeting on Reaction Engineering and ProcessNet Subject Division Heat and Mass Transfer 2022, Würzburg, 2022, poster presentation.

  • Frey, T.; Hoffmann, M.; Schlüter, M.: "A DNS Approach to high-Schmidt-Number problems in Reactive Micro- and Milli Systems". NAMF Mixing XXVII, virtual, 2022, poster presentation.

  • Schwarz, S.; Frey, T.; Hoffmann, M.; Biessey, P.; Schlüter, M.; Grünewald, M: "Compartmentmodellierung von statischen Mischelementen mithilfe der Mean-Age Theorie". Jahrestreffen der ProcessNet-Fachgemeinschaft "Prozess-, Apparate- und Anlagentechnik", virtual, 2021, poster presentation.

  • Frey, T.; Schwarz, S.; Seithümmer, V.; Bissey, P.; Hoffmann, M.; Grünewald, M.; Schlüter, M.: "Numerische Strömungssimulation zum Einfluss auf den Umsatz und die Selektivität einer Polymerisationsreaktion". Jahrestreffen der ProcessNet-Fachgemeinschaft "Prozess-, Apparate- und Anlagentechnik", virtual, 2020, poster presentation.

Publications

[189724]
Title: Advances in Characterization of Industrial Bioreactors for Cell Culture Process. <em>Biopharmaceutical Manufacturing</em>
Written by: Fitschen, J.; Hofmann, S.; Kursula, L.; Haase, I.; Wucherpfennig, T.; Schlüter, M.
in: <em>Biopharmaceutical Manufacturing</em>. (2024).
Volume: Number:
on pages:
Chapter: 3
Editor: In Pörtner, Ralf (Eds.)
Publisher: Springer International Publishing:
Series:
Address:
Edition:
ISBN: 978-3-031-45668-8
how published:
Organization:
School:
Institution:
Type:
DOI: 10.1007/978-3-031-45669-5
URL:
ARXIVID:
PMID:

Note:

Abstract: Aerated stirred tank reactors are widely used in the biopharmaceutical industry for cell culture applications due to their flexibility and broad range of uses. This book chapter provides an overview of the main characterization methods for aerated stirred tank reactors in the context of cell culture processes. The methods described include mechanical power input, volumetric mass transfer, flow field, and mixing characterization. Examples are given using stirred tank reactors of different scales, ranging from a 3 L laboratory scale to a 15,000 L industrial scale. The chapter also discusses recent developments in the use of mobile, encapsulated sensors known as Lagrangian Sensor Particles (LSP) for continuous data collection and transmission throughout the entire reactor volume, providing insights from the perspective of cells during a cell culture process. Additionally, the state-of-the-art in numerical flow simulation is discussed, using aerated stirred tank reactors as an example to illustrate the challenges and opportunities offered by numerical flow simulation. It is highlighted that the methods described are specifically focused on cell culture applications, which have lower specific power inputs and aeration rates compared to other types of applications such as microbial fermentations or chemical reactions. The chapter also provides a brief overview of the fundamentals of aerated stirred tank reactors, including their design and components, and emphasizes the importance of equipment characterization for successful process transfer and scaleup in cell culture processes.

Frans Jan de Jong

Dr.-Ing. Frans Jan de Jong

2010 - 2015        Research Fellow at the IMS

Research Expertise

Influence of boundary layer flows on the structure of macromolecules fixed to a flat plate


Ingrid Haase

Ingrid Haase, M.Sc.

2020-2023       Research Fellow at the IMS

Research Expertise

Large Scale Bioreactors - Insight Into a Black Box


 

Sebastian Hofmann

Sebastian Hofmann, M.Sc.


Eißendorfer Str. 38

Building O, Room 3.018

21073 Hamburg

Phone +49 40 42878 - 3106

Mail Sebastian Hofmann


Research

DFG Priority Program SPP 2170 “InterZell” – Project “CHOLife”: Multiscale experimental analysis and simulation of lifelines in bioreactors to study their impact on the cultivation performance of Chinese Hamster Ovary (CHO) cells

Large-scale bioreactors with working volumes up to 22,000 L are frequently exposed to dynamic cultivation conditions that create spatial and temporal gradients in mixing. These variations cause a decline in cellular performance, which ultimately results in lower product quality and quantity. Precise and reliable process control is critical for biopharmaceutical production of vaccines and monoclonal antibodies, as well as for understanding the impact of dynamically changing environments on cells. For the detailed understanding of cultivation processes it is indispensable to get deep insights into the overall and local hydrodynamics with high spatial and temporal resolution.

CHOLife tackles the scale-up problem linking the unique access to a transparent 15,000 L cell culture bioreactor (Institute of Multiphase Flows, TUHH Hamburg, IMS) with the development of a novel scale-up device (Institute of Biochemical Engineering, Stuttgart, IBVT) in order to predict industrial-scale performance of IgG1 producing CHO cells. In essence, three dimensional flow trajectories and lifelines will be measured at the IMS and mimicked in the novel scale-up simulator of IBVT. The close cooperation of both parties ensures a successful scale-down of large-scale conditions and an equally successful prediction of large-scale performance of CHO cells cultured in the novel scale-up simulator.

One method of gaining insight into complex hydrodynamic flow patterns and compartmentalization is by means of the (de)colorization method, which is based on phenolphthalein or bromothymol blue in an acrylic glass bioreactor. However, the lack of optical access into generic bioreactors requires an alternative analysis. Industrially used fixed probes at the reactor wall cannot provide information on spatiotemporal gradients or the cell's residence time in different zones of the reactor.

To overcome this limitation, Lapin et al. proposed the "Traveling along the Lifelines of Single Cells" approach, which uses a numerical method. This Lagrangian analysis was recently experimentally scrutinized on laboratory-scale through the 4D-Particle Tracking Velocimetry (4D-PTV) method demonstrating detailed results regarding the flow-following capability of Lagrangian particles.

On production scale, a combination of sensor systems integrated into a mobile, enclosed and neutrally buoyant Lagrangian Sensor Particle (LSP) offers a deeper understanding of complex flow patterns inside a bioreactor by recording data alongside its trajectory and thereby mimicking the movement of a cell.

Science Communication
Awards
  • Maximilian Kamp as the winner of the “Karl H. Ditze Award of the TUHH to graduates of the TUHH” in the category of outstanding Bachelor thesis. The thesis convinced the committee in terms of theoretical-scientific quality, practical relevance and interdisciplinarity, which was written within the framework of the priority program SPP 2170 “InterZell” (funded by the DFG).

  • Winner of the I3 Junior Project: Flow-following Lagrangian Sensor Particles - Development of a novel measurement technique with conductivity sensors for a novel macro-mixing and lifeline analysis; Hofmann, S.; Kamp, M.; Buntkiel, L.; Reinecke, S.; I3-Programm, sponsored by the Hamburg University of Technology for the project period 01/2023 - 03/2024

Research Projects
  • DFG Priority Program 2170 – InterZell – CHOLife
Education

Undergraduate courses

  • Reactor Design Using Local Transport Processes (Winter Semester 2022/23)

  • Reactor Design Using Local Transport Processes (Winter Semester 2021/22)

  • Grundlagen des Technischen Zeichnens (Summer Semester 2021)

Supervised Theses

  • "Effect of a Phosphate-Buffered System on the Determination of the Volumetric Mass Transfer Coefficient kLa for CO2", Lara Offermann, Bachelor thesis (supervision in cooperation with Marc Maly and Nicolas Nickel), 2024

  • "Measurement and modelling of carbon dioxide and oxygen partial pressures over the height of a 15,000 L acrylic glass reactor", working title, Noah von Schnitzler, Master thesis (supervision in cooperation with Marc Maly and Nicolas Nickel), 2024

  • "Development, Implementation and Testing of a Technical Solution for the Determination of Gas Partial Pressures at Different Heights of an Aerated Stirred Tank Reactor on Industrial Scale", Noah von Schnitzler, project work (supervision in cooperation with Marc Maly and Nicolas Nickel), 2024

  • "Lagrangian Sensor Particles in a 15,000 L Bioreactor: Experimental Comparison of Different Sizes on their Flow-Following Capability", Isabel Sophie Brouwers, Master's Thesis, 2024: Thesis available here and Python code available here.

  • "Überblick und Bewertung von Bioprozesssensoren in Lagrangeschen Sensor Partikeln: Stand der Technik, Miniaturisierung und Weiterentwicklung", Julius Plock, Bachelor's Thesis, 2023

  • "Experimental Investigations of the Flow-Following Capabilities and Hydrodynamic Characteristics of Lagrangian Sensor Particles with Respect to their Centre of Mass", Ryan Rautenbach, Master's Thesis, 2023: Python evaluation code available here.

  • "Experimental investigation of the flow behavior of Lagrangian LED Particles in a 200 l bioreactor", Maximilian Kamp, Bachelor's Thesis, 2022: Thesis available here and MATLAB code available here.

  • "Design, Construction and Evaluation of Lagrangian Sensor Particles for the Flow Behavior Determination in a 200 L and 15000 L Bioreactor", Paramveer Singh GopalSingh, Master's Thesis, 2023: Thesis available here and MATLAB and C++ code available here.

  • "Experimental Characterization of Modified Polyurethane Foams for Mechanical Clean Up of Oil Pollutants at Sea Surface" (in close cooperation with Daniel Niehaus), Srividya Kumar Bairamangala, Project Work, 2020-2021

Oral and Poster Presentations

Lectures

  • Hofmann, S.; Buntkiel, L.; Rautenbach, R.; Hampel, U,; Schlüter, M.: Comparing Trajectories from Lagrangian Sensor Particles and Lattice-Boltzmann Simulations in a 15,000 L Bioreactor, Mixing XXVIII & ISMIP 11 Conference, Banff, Alberta, Canada, 2024, Presentation
  • Rautenbach, R.; Hofmann, S.; Buntkiel, L.; Barczyk, J.; Hoffmann, M.; Reinecke, S.; Takors, R.; Hampel, U.; Schlüter, M.: Simulation of Lagrangian Sensor Particles as Resolved Particles in an Industrial Bioreactor through Lattice-Boltzmann Large Eddy Simulations, 28th International Symposium on Chemical Reaction Engineering, Turku, Finland, 2024, Presentation
  • Rautenbach, R.; Hofmann, S.; Buntkiel, L.; Barczyk, J.; Reinecke, S.; Hoffmann, M.; Takors, R.; Hampel, U.; Schlüter, M.: Resolved Particle Lattice-Boltzmann Large Eddy Simulation in a 15,000 L Bioreactor to mimic Lagrangian Sensor Particles, 8th BioProScale Symposium, Berlin, Germany, 2024, Presentation
  • Hofmann, S.; Buntkiel, L.: Best Practices in Research Software Engineering: Working with MATLAB and Gitlab, 2nd "Technical Baldyga Seminar", 3rd "Mixing Meets Reality" Conference, Berlin, Germany, 2023, Presentation
  • Hofmann, S.; Buntkiel, L.; GopalSingh, P.; Fitschen, J.; Hoffmann, M.; Reinecke, S.; Hampel, U,; Schlüter, M.: Experimental Investigation of Circulation Times with Lagrangian Sensor Particles in a 15,000 L Acrylic Glass Reactor, 17th European Conference on Mixing (MIXING 17), Porto, Portugal, 2023, Presentation
  • Hofmann, S. - Lagrangian Particles: Experimental Determination of Lifelines in a 3 L and 15000 L Stirred Tank Reactor, Biobased Process and Reactor Technologies PhD Seminar, Hamburg University of Technology, Hamburg, 2022, Presentation
  • Hofmann, S.; Gaugler, L.: CHOLife - Multiscale Experimental Analysis and Simulation of Lifelines in Bioreactors to Study their Impact on the Cultivation Performance of CHO Cells, Annual Meeting: Priority Program Status Meeting of the SPP2170 "InterZell", organized by Uni Stuttgart, Stuttgart, 2022, Presentation
  • Fitschen, J.; Kuschel, M.; Hofmann, S.; Wucherpfennig, T.; v. Kameke, A.; Hoffmann, M.; Schlüter, M.: Characterization of Heterogeneities in Stirred Tank Reactors by Means of 4D Particle Trajectories and Numerical Flow Simulations, MIXING XXVII, North American Mixing Forum (NAMF), Online Conference 2022, Presentation
  • Hofmann, S.; Vernier-Lambert, H.; Meriguet, S.; GopalSingh, P.; Fitschen, J.; Neubauer, P.; von Lieres, E.; Ferguson, M.; Schlüter, M.: Assessment of Lagrangian Sensor Particle Designs in a Transparent 15,000 L Acrylic Glass Bioreactor, 7th BioProScale Symposium, organized by Prof. Neubauer (TU Berlin), Langenbeck-Virchow-Haus, Berlin 2022, Presentation
  • Gaugler, L.; Mast, Y.; Fitschen, J.; Hofmann, S.; Schlüter, M.; Takors, R.: Development of a single multi-compartment bioreactor (SMCB) for CHO scale-down studies in a heterogeneous cultivation environments, 7th BioProScale Symposium, organized by Prof. Neubauer (TU Berlin), Langenbeck-Virchow-Haus, Berlin 2022, Presentation
  • Weiland, C; Hofmann, S.; Fitschen, J.; von Kameke, A.; Hoffmann, M.; Schlüter, M.: Numerische Simulation Lagranger Partikeltrajektorien und Charakterisierung des Partikelfolgevermögens in einem 3 L Rührkesselreaktor, Jahrestreffen der ProcessNet-Fachgruppen Computational Fluid Dynamics + Mischvorgänge + Agglomerations- und Schüttguttechnik, DECHEMA, Hyperion Hotel Leipzig, 2022, Presentation
  • Fitschen, J.; Hofmann, S.; Hoffmann, M.; Kuschel, M.; Wucherpfennig, T.; Schlüter, M.: Lokale Mischzeitverteilung in begasten Rührkesselreaktoren im Labormaßstab, Jahrestreffen der ProcessNet-Fachgruppen Computational Fluid Dynamics + Mischvorgänge + Agglomerations- und Schüttguttechnik, DECHEMA, Hyperion Hotel Leipzig, 2022, Presentation
  • Hofmann, S.; Weiland, C.; Fitschen, J.; v. Kameke, A.; Hoffmann, M.; Schlüter, M.: Vergleich von experimentellen und numerischen Untersuchungen zur Abschätzung des Folgevermögens verschiedener Lagrange’scher Partikel in der Bioreaktorströmung, Jahrestreffen der ProcessNet-Fachgruppen Computational Fluid Dynamics + Mischvorgänge + Agglomerations- und Schüttguttechnik, DECHEMA, Hyperion Hotel Leipzig, 2022, Presentation
  • Hofmann, S.; Gaugler, L.; Fitschen, J.; v. Kameke, A.; Schlüter, M.; Takors, R.: Lagrangian Particle Tracking and Bioreactor Compartmentalization as Novel Scale-up Tools for Biopharmaceutical Processes, 13th European Congress of Chemical Engineering, 6th European Congress of Applied Biotechnology (ECCE 13 & ECAB 6), DECHEMA, Online conference, 2021, Presentation
  • Fitschen, J.; Kuschel, M.; Hofmann, S.; Hoffmann, H.; von Kameke, A.; Wucherpfennig, T.; Wutz, J.; Schlüter, M.: Validation of Numerical Flow Simulations in a 3 L Stirred Tank by Means of Real 4D Particle Trajectories 13th European Congress of Chemical Engineering, 6th European Congress of Applied Biotechnology (ECCE 13 & ECAB 6), DECHEMA, Online conference, 2021, Presentation
  • Fitschen, J.; Hofmann, S.; Hoffmann, H.; von Kameke, A.; Schlüter, M.: Measurement of Lagrangian Tracks in a 3 L Stirred Tank Reactor using 4D Particle Tracking Velocimetry with Shake-the-Box, ISPIV 21 (virtual), 2021, Presentation
  • Fitschen, J.; Kuschel, M.; Hofmann, S.; Hoffmann, H.; von Kameke, A.; Wucherpfennig, T.; Wutz, J.; Schlüter, M.: Validierung von numerischen Strömungssimulationen in einem 3L Rührkesselreaktor mittels 3D Partikel Trajektorien, Jahrestreffen der ProcessNet-Fachgruppen Computational Fluid Dynamics und Mehrphasenströmungen, 2021, Plenary Lecture
  • Hofmann, S.; Gaugler, L.: CHOLife - Multiscale Experimental Analysis and Simulation of Lifelines in Bioreactors to Study their Impact on the Cultivation Performance of CHO Cells, 2nd Annual Priority Program Status Meeting of the SPP2170 "InterZell", organized by Uni Stuttgart, Koblenz, 2021, Presentation

Poster Presentations

  • Hofmann, S.: Experimental Determination of Compartments in a 15,000 L Acrylic Glass Bioreactor by Means of Lagrangian Sensor Particles, Biobased Process and Reactor Technologies PhD Seminar, Hamburg University of Technology, Hamburg, 2022, Poster Presentation

  • Hofmann, S.; Buntkiel, L.; Reinecke, S.; GopalSingh, P.; Fitschen, J.; Hoffmann, M.; Hampel, U.; Schlüter, M.: Experimentelle Charakterisierung unterschiedlicher Lagrangescher Sensor Partikel Designs in einem 15000 L Bioreaktor, 16. Dresdner Sensor-Symposium, Dresden, 2022, Poster Presentation

  • Hofmann, S.; Weiland, C.; GopalSingh, P.; Kamp, M.; Fitschen, J.; v. Kameke, A.; Hoffmann, M.; Schlüter, M.: Experimental and Numerical Determination of Lifelines in a 3 L, 200 L and 15000 L Stirred Tank Reactor to Estimate the Flow-Following Capability of Lagrangian Sensor Particles, FTZ 3i Talk: Conference on intelligent - industrial - innovations, HAW Hamburg 2022, Poster Presentation

  • Hofmann, S.; Weiland, C.; GopalSingh, P.; Kamp, M.; Fitschen, J.; v. Kameke, A.; Hoffmann, M.; Schlüter, M.: Experimental and Numerical Determination of Lifelines in a 3 L, 200 L and 15000 L Stirred Tank Reactor to Estimate the Flow-Following Capability of Lagrangian Sensor Particles, 4th International Symposium on Multiscale Multiphase Process Engineering (MMPE), Berlin 2022, Poster Presentation

  • Hofmann, S.; Weiland, C.; GopalSingh, P.; Kamp, M.; Fitschen, J.; v. Kameke, A.; Hoffmann, M.; Schlüter, M.: Experimental and numerical determination of lifelines in a 3 L, 200 L and 15000 L stirred tank reactor, MIXING XXVII, North American Mixing Forum (NAMF), Online Conference 2022, Poster Presentation

  • Hofmann, S.; Fitschen, J.; v. Kameke, A.; Schlüter, M.: Multiscale Experimental Analysis of Lifelines in Bioreactors 1. Hamburg-Bochumer Mehrphasensymposium, Hamburg/Bochum, Online Conference, 2020, Poster Presentation

Publications

[189724]
Title: Advances in Characterization of Industrial Bioreactors for Cell Culture Process. <em>Biopharmaceutical Manufacturing</em>
Written by: Fitschen, J.; Hofmann, S.; Kursula, L.; Haase, I.; Wucherpfennig, T.; Schlüter, M.
in: <em>Biopharmaceutical Manufacturing</em>. (2024).
Volume: Number:
on pages:
Chapter: 3
Editor: In Pörtner, Ralf (Eds.)
Publisher: Springer International Publishing:
Series:
Address:
Edition:
ISBN: 978-3-031-45668-8
how published:
Organization:
School:
Institution:
Type:
DOI: 10.1007/978-3-031-45669-5
URL:
ARXIVID:
PMID:

Note:

Abstract: Aerated stirred tank reactors are widely used in the biopharmaceutical industry for cell culture applications due to their flexibility and broad range of uses. This book chapter provides an overview of the main characterization methods for aerated stirred tank reactors in the context of cell culture processes. The methods described include mechanical power input, volumetric mass transfer, flow field, and mixing characterization. Examples are given using stirred tank reactors of different scales, ranging from a 3 L laboratory scale to a 15,000 L industrial scale. The chapter also discusses recent developments in the use of mobile, encapsulated sensors known as Lagrangian Sensor Particles (LSP) for continuous data collection and transmission throughout the entire reactor volume, providing insights from the perspective of cells during a cell culture process. Additionally, the state-of-the-art in numerical flow simulation is discussed, using aerated stirred tank reactors as an example to illustrate the challenges and opportunities offered by numerical flow simulation. It is highlighted that the methods described are specifically focused on cell culture applications, which have lower specific power inputs and aeration rates compared to other types of applications such as microbial fermentations or chemical reactions. The chapter also provides a brief overview of the fundamentals of aerated stirred tank reactors, including their design and components, and emphasizes the importance of equipment characterization for successful process transfer and scaleup in cell culture processes.

Sven Kastens

Dr.-Ing. Sven Kastens

2013 - 2018        Research Fellow at the IMS

Research Expertise

  • Experimental Investigation of Reactive Bubbly Flows - Influence of Boundary Layer Dynamics on Mass Transfer and Chemical Reactions (DFG Priority Project 1740)

  • Experimental investigation and modeling of local mass transfer rates in pure and contaminated Taylor flows (DFG Priority Project 1506)


Florian Kopf

Dr.-Ing. Florian Kopf

2010 - 2013        Research Fellow at the IMS

Research Expertise

Computational fluid dynamics and experimental analysis of transport phenomena in micro-bioreactors


Katrin Laqua

Dipl.-Ing. Katrin Laqua

2011 - 2017        Research Fellow at the IMS

Research Expertise

  • Experimental study of multiphase flows under extreme environmental conditions in combination to the oil spill 2010 in the Gulf of Mexico (C-IMAGE)

  • Description of the fluid pathways of a deep-sea blowout: From multiphase petroleum jet to a rising plume, to bubbles and drops

  • Description of methane hydrate formation

  • Determination of the bubble and drop size distribution with endoscopic Particle Image Velocimetry (PIV)

  • Determination of the physical properties and the composition of the multiphase mixture


Marc Maly

Marc Maly, M.Sc.


Marc Maly, M.Sc.

2019 - 2024        Research Fellow at the IMS

2023 - 2024        Head of working group "Industrial Research Projects"

Research Expertise

Scaling and Industrial Application of (Jet) Loop Reactors


 

Biography

Marc Maly studied at Hamburg University of Technology (TUHH) from 2012 to 2015 in the bachelor's programme Energy and Environmental Engineering. Following his Bachelor Thesis, Marc Maly started working as a student assistant at the Institute of Multiphase Flows (IMS). From 2015 on he attended the master’s programme Renewable Energy at TUHH and graduated at the end of 2018.

After graduating, he started working for TuTech Innovations GmbH in 2019 and was employed at the IMS as a research assistant. There he took care of the industrial research projects of the institute until June 2024.

From November 2023 on, Marc Maly was the group leader of the working group Industrial Research Projects, which closely cooperates with the research groups Multiphase Flows in Bioreactors and Reactive Bubbly Flows at IMS.

Research

Several cooperative research projects are conducted by the Institute of Multiphase Flows (IMS) with partners from different industries. In past projects, Marc Maly has worked on the topics of three-phase-operated loop reactors in the chemical industry and stirred tank reactors, as used for example in the pharmaceutical industry.

A pilot-scale airlift loop reactor was designed for experiments with liquid, gaseous and solid phases. The discharge of the solid phase was of particular importance. For investigations in a stirred tank reactor, an acrylic twin of a commercially available reactor was designed and manufactured at IMS. A wide range of measurements were conducted in close cooperation with Jürgen Fitschen to gather information on various phenomena (bubble size distributions, mass transfer etc.). Further investigations for even deeper insights into selected topics are carried out in a follow-up project by Vincent Bernemann.

Eventually, Marc Maly worked on a project which is concerned with the transferal and optimisation of a decade-old implementation of an agrochemical process to a multiphase jet loop reactor system. While measurements are conducted at the IMS in different scales in a water/air-system, the project partner simultaneously investigates the original material system in a provided, scaled-down laboratory reactor. The experiments across scales and material systems provide insight into the transfer of different phenomena between systems sizes. The gathered data forms the basis for a future scale-up of the process to levels above pilot-plant scale.

Cover Story of Processes

We are honoured that our open access research article “Scale-Up Strategies of Jet Loop Reactors for the Intensification of Mass Transfer Limited Reactions” is represented as the cover story of the Processes issue of August 2022 (Volume 10, Issue 8). The complete issue can be found here, the featured article here.

The featured article covers the design and scaling of a laboratory-scale jet loop reactor for the investigation of the intensification of an existing industrial-scale gas-liquid process. As existing process operation data from a bubble column hint at a mass transfer limitation of the gas-liquid reaction, a jet loop reactor (JLR) is chosen to increase the specific interfacial area between gas and liquid and thus increase mass transfer in the process.

The presented work shows that the JLR concept can be transferred sufficiently well between different scales when suitable parameters are chosen, and offers a wide operating window. The investigations aim to provide a basis for a future scale-up of the chemical process in the JLR system to the industrial scale.

Education

Undergraduate and Graduate Teaching Assistant

  • Grundlagen des Technischen Zeichnens (summer semester 2021)

  • Konstruktion und Apparatebau (winter semester 2021/2022)

  • Konstruktion und Apparatebau (winter semester 2022/2023)

  • Einführung in CAD (winter semester 2023/2024)

 


Supervised Theses

  • "Effect of a Phosphate-Buffered System on the Determination of the Volumetric Mass Transfer Coefficient kLa for CO2", Lara Offermann, Bachelor thesis (supervision in cooperation with Sebastian Hofmann and Nicolas Nickel), 2024

  • "Measurement and modelling of carbon dioxide and oxygen partial pressures over the height of a 15,000 L acrylic glass reactor", working title, Noah von Schnitzler, Master thesis (supervision in cooperation with Nicolas Nickel and Sebastian Hofmann), 2024

  • "Development, Implementation and Testing of a Technical Solution for the Determination of Gas Partial Pressures at Different Heights of an Aerated Stirred Tank Reactor on Industrial Scale", Noah von Schnitzler, project work (supervision in cooperation with Sebastian Hofmann and Nicolas Nickel), 2024

  • "Bereitstellung regenerativer Energie aus Abwasserwärme zur nachhaltigen Sanierung eines Großpumpwerkes", Atousa Jalilian, Master thesis (supervision of external thesis at Hamburg Wasser, supervisors at Hamburg Wasser: B. Büttner and S. Stenbuck), 2023

  • "Development of a Method for the Experimental Determination of the Circulation Gas Fraction in Jet Loop Reactors", Karolina Piernikowski, Master thesis, 2023

  • "Experimental Investigation and Classification of the Mass Transfer Coefficient of Different Aeration Devices in the 3 L Stirred Tank Reactor Under Consideration of the Bubble Formation", Jannick Krause, Bachelor thesis (supervision in cooperation with Ingrid Haase), 2023

  • "Experimental Investigation of the Influence of Modified Agitators on the Power Input and Oxygen Mass Transfer in a 30 Liter Stirred Tank Reactor", Josefine Velde, project work (supervision in cooperation with Ingrid Haase), 2023

  • "Prototyping, Implementation and Investigation of an Additional Aerator for a Jet Loop Reactor in Form of a Flange Module", Sweta Shamria, project work, 2023

  • "Implementation of a Process for the Oxidation of Biomass to Formic Acid in a Jet Loop Reactor", Malte Maßmann, Master thesis (external thesis at Universität Hamburg, supervision in cooperation with Sebastian Eller), 2023

  • "Experimental Investigation and Optimisation of the Geometry of a Two-Phase Nozzle in a Jet Loop Reactor", Merle Wohlberg, Bachelor thesis, 2022

  • "Study of Storage Stability in Relation to Moisture Diffusion and Temperature in Automatic Dish Washing Tablets", Srividya Bairamangala, Master thesis (supervision of external thesis at Henkel AG & Co. KGaA; supervisor at Henkel AG & Co. KGaA: A. Gebert), 2022

  • "Design of a Pressure- and Chemical-Resistant Jet-Loop Reactor by Scale-Down from Pilot-Plant to Laboratory Scale and Subsequent Characterisation", Steffen Schaper, Master thesis, 2021

  • "Experimental Determination of the Oxygen Mass Transfer Performance and the Bubble Size Distribution of a 200 L Single-Use Aerated Stirred Tank Reactor", Rajat Srivastava, Master thesis (supervision in cooperation with Jürgen Fitschen), 2021

  • "Experimental Analysis of the Solids Discharge in a Three-Phase Operated Airlift Loop Reactor", Anna-Christin Menzel, Bachelor thesis, 2020

 


Committees

 


Supervised Student Assistants

  • Timo Scherwinski, 03/2019 - 06/2019

  • Anna Menzel, 10/2019 - 06/2023

  • Anahita Radmehr, 03/2020 - 06/2022

  • Steffen Schaper, 09/2020 - 11/2020
  • Helena Ostrinsky, 07/2023 - 06/2024

  • Jakob Schulze, 07/2023 - 06/2024

  • Noah von Schnitzler, 10/2023 - 04/2024

  • Jannick Krause, 11/2023 - 06/2024

Poster and Oral Presentations

Oral Presentations

  • Maly, M.; Kuwertz, R.; Heck, J.; Schlüter, M.: Scale-Up Investigations of a Jet Loop Reactor for the Implementation of a Chemical Process in an Alternative Reactor Concept, 11th International Conference on Multiphase Flow, Kobe, Japan, 2023, oral presentation

  • Maly, M.: Investigations for the Transfer and Intensification of an Agrochemical Process, PhD Student Seminar of FSP Environmental & Energy Systems, 2023, oral presentation

  • Pesch, S., Radmehr, A., Knopf, R., Maly, M., Paris, C. B., Perlin, N., et al.: Investigation of Droplet Dispersion and Distribution in Experiments and Modeling: Relevant Findings for Decision-Making and Dispersant Use, Gulf of Mexico Oil Spill & Ecosystem Science Conference, Tampa, FL, 2020, oral presentation

  • Pesch, S.; Maly, M.; Jaeger, P.; Malone, K.; Krause, D.; Schlüter, M.: Experimental Investigation of the Rise Behavior of Live-Oil Droplets during Deep-Sea Oil Spills, Advancing Oil Spill Research, Part 2, Webinar, Marine Technology Society (MTS), 2018, oral presentation

  • Pesch, S.; Maly, M.; Jaeger, P.; Malone, K.; Krause, D.; Schlüter, M.: Experimental Investigation of the Rise Behavior of Gas-Saturated Crude-Oil Droplets under High Pressure, 6th Gulf of Mexico Oil Spill and Ecosystem Science Conference, New Orleans, LA, 2018, oral presentation

  • Maly, M.; Pesch, S.; Schlüter, M.: Die Tiefsee im Labor – Wie eine Ölkatastrophe an der TUHH erforscht wird, 2. Maritime Nacht an der TUHH, Hamburg, Germany, 2018, oral presentation

Poster Presentations

Publications

[189724]
Title: Advances in Characterization of Industrial Bioreactors for Cell Culture Process. <em>Biopharmaceutical Manufacturing</em>
Written by: Fitschen, J.; Hofmann, S.; Kursula, L.; Haase, I.; Wucherpfennig, T.; Schlüter, M.
in: <em>Biopharmaceutical Manufacturing</em>. (2024).
Volume: Number:
on pages:
Chapter: 3
Editor: In Pörtner, Ralf (Eds.)
Publisher: Springer International Publishing:
Series:
Address:
Edition:
ISBN: 978-3-031-45668-8
how published:
Organization:
School:
Institution:
Type:
DOI: 10.1007/978-3-031-45669-5
URL:
ARXIVID:
PMID:

Note:

Abstract: Aerated stirred tank reactors are widely used in the biopharmaceutical industry for cell culture applications due to their flexibility and broad range of uses. This book chapter provides an overview of the main characterization methods for aerated stirred tank reactors in the context of cell culture processes. The methods described include mechanical power input, volumetric mass transfer, flow field, and mixing characterization. Examples are given using stirred tank reactors of different scales, ranging from a 3 L laboratory scale to a 15,000 L industrial scale. The chapter also discusses recent developments in the use of mobile, encapsulated sensors known as Lagrangian Sensor Particles (LSP) for continuous data collection and transmission throughout the entire reactor volume, providing insights from the perspective of cells during a cell culture process. Additionally, the state-of-the-art in numerical flow simulation is discussed, using aerated stirred tank reactors as an example to illustrate the challenges and opportunities offered by numerical flow simulation. It is highlighted that the methods described are specifically focused on cell culture applications, which have lower specific power inputs and aeration rates compared to other types of applications such as microbial fermentations or chemical reactions. The chapter also provides a brief overview of the fundamentals of aerated stirred tank reactors, including their design and components, and emphasizes the importance of equipment characterization for successful process transfer and scaleup in cell culture processes.

Simon Matthes

Dr.-Ing. Simon Matthes

2017 - 2021        Research Fellow at the IMS

Research Expertise

Characterization of Fine Bubbles for Biocatalytic Processes


Christoph Meyer

Dipl.-Ing. Christoph Meyer

2010 - 2015        Research Fellow at the IMS

Research Expertise

  • Experimental investigation and modeling of local mass transfer rates in pure and contaminated Taylor flows (SPP-1506)

  • Study of transport processes at fluidic interfaces on microscale

  • Investigation of local mass transfer rates measuring the velocity and concentration fields simultaneously

  • Analysis of the local velocity field by micro-particle image velocimetry (µ-PIV) and local concentration field by laser-induced fluorescence (LIF) respectively

  • Investigation and influence of contaminations and surfactants on mass transfer

  • Modeling of local mass transfer rates of fluidic interfaces


Stefan Mosler

Dipl.-Math. Stefan Mosler

2010 - 2014        Research Fellow at the IMS

Research Expertise

Modelling, simulation and experimental analysis of two-phase flows in a Y-Y shaped microreactor


Christian-Ole Möller

Dipl.-Ing. Christian-Ole Möller

2012 - 2016        Research Fellow at the IMS

Research Expertise

  • Energy efficient multiphase processes

  • Development of novel structured packings

  • Mass transfer enhancement of multiphase apparatuses

  • Energy efficiency enhancement of multiphase apparatuses

  • Optimization of bubble column reactors

  • Experimental studies of hydrodynamics and mass transfer processes in multiphase apparatuses

Daniel Niehaus

Daniel Niehaus, M.Sc.

2019 - 2024        Research Fellow at the IMS

Research Expertise

Construction and characterisation of aerated biotechnological high-pressure reactors within the framework of the Protein Pressure Stability Impact (Prot. P.S.I.)


Simeon Pesch

Dr.-Ing. Simeon Pesch

2015 - 2020        Research Fellow at the IMS

Research Expertise

  • Center for the Integrated Modeling and Analysis of Gulf Ecosystems (C-IMAGE II, C-IMAGE III)

  • Experimental investigation and modeling of multiphase flow phenomena under extreme environmental conditions in relation to the deep-sea oil spill 2010 in the Gulf of Mexico


Steffen Richter

Dipl.-Wi.-Ing. Steffen Richter

2009 - 2018        Research Fellow at the IMS

Research Expertise

Industrial research for multiphase flow systems


Annika Rosseburg

Dr.-Ing. Annika Rosseburg

2013 - 2018        Research Fellow at the IMS

Research Expertise

  • Aerated stirred tank reactors

  • Scale-up and scale-down

  • Investigation of local and global flow structure, bubble size distribution, gas hold-up and mixing


Sophie Rüttinger

Dr.-Ing. Sophie Rüttinger

2014 - 2019        Research Fellow at the IMS

Research Expertise

Investigation of the influence of vortex structures on transport processes at fluidic interfaces (Priority Program 1740)


Claas Spille

Claas Spille, M.Sc.

2017 - 2021 Research Fellow at the IMS

Research Expertise


Nicolai Szeliga

Dr.-Ing. Nicolai Szeliga

2014 - 2019        Research Fellow at the IMS

Research Expertise

Safety-relevant analysis of the performance of centrifugal pumps, valves and inlet geometries, including stress-related events (SAVE)


Jens Timmermann

Dr.-Ing. Jens Timmermann

2012 - 2017        Research Fellow at the IMS

Research Expertise

Experimental Investigation of Reactive Bubbly Flows - Influence of Boundary Layer Dynamics on Mass Transfer and Chemical Reactions


Christian Urban

Dr.-Ing. Christian Urban

2011 - 2014        Research Fellow at the IMS

Research Expertise

CIWA - Condensation Induced Water Hammer