M.Sc.

Nießing, Bastian

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  • Publication
    Automated Production at Scale of Induced Pluripotent Stem Cell-Derived Mesenchymal Stromal Cells, Chondrocytes and Extracellular Vehicles: Towards Real-Time Release
    ( 2023-10-10)
    Herbst, Laura
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    Groten, Ferdinand
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    Murphy, Mary
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    Shaw, Georgina
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    Nießing, Bastian
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    Schmitt, Robert H.
    Induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) are amenable for use in a clinical setting for treatment of osteoarthritis (OA), which remains one of the major illnesses worldwide. Aside from iPSC-derived iMSCs, chondrocytes (iCHO) and extracellular vesicles (EV) are also promising candidates for treatment of OA. Manufacturing and quality control of iPSC-derived therapies is mainly manual and thus highly time consuming and susceptible to human error. A major challenge in translating iPSC-based treatments more widely is the lack of sufficiently scaled production technologies from seeding to fill-and-finish. Formerly, the Autostem platform was developed for the expansion of tissue-derived MSCs at scale in stirred tank bioreactors and subsequent fill-and-finish. Additionally, the StemCellDiscovery platform was developed to handle plate-based cultivation of adherent cells including their microscopic analysis. By combining the existing automation technology of both platforms, all required procedures can be integrated in the AutoCRAT system, designed to handle iPSC expansion, differentiation to iMSCs and iCHOs, pilot scale expansion, and formulation of iMSCs as well as extracellular vesicles and their purification. Furthermore, the platform is equipped with several in-line and at-line assays to determine product quality, purity, and safety. This paper highlights the need for adaptable and modular automation concepts. It also stresses the importance of ensuring safety of generated therapies by incorporating automated release testing and cleaning solutions in automated systems. The adapted platform concepts presented here will help translate these technologies for clinical production at the necessary scale.
  • Publication
    LIFTOSCOPE: automatisierte Highspeed-Zelluntersuchung und -transfer
    ( 2023-09-17)
    Nienhaus, Florian orcid-logo
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    Aurich, Ann-Sophie
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    Nießing, Bastian
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    Schmitt, Robert H.
    Analysis and isolation of cell cultures play a decisive role in biological processes. Currently, these steps are often performed manually, which is time-consuming. Additionally, for each step a separate device is required. The aim of LIFTOSCOPE is to automate these processes in just one device. It combines three functional principles: high-speed microscopy, image analysis and laser-induced forward transfer. A prototype was successfully developed to demonstrate the feasibility of this concept.
  • Publication
    Towards automated CAR-T Cell Manufacturing. Keeping up with Technological Advancement
    ( 2023-05-04)
    Herbst, Laura
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    Erkens, Frederik
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    Hort, Simon orcid-logo
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    Bäckel, Niklas
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    Nießing, Bastian
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    Popp, Georg
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    Franz, Paul
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    König, Niels orcid-logo
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    Hudecek, Michael
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    Rafiq, Qasim
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    Goldrick, Stephen
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    Papantoniou, Ioannis
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    Schmitt, Robert H.
    The AIDPATH project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement no 101016909. The material presented and views expressed here are the responsibility of the author(s) only. The EU Commission takes no responsibility for any use made of the information set out.
  • Publication
    Adaptive phase contrast microscopy to compensate for the meniscus effect
    ( 2023-04-08)
    Nienhaus, Florian orcid-logo
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    Piotrowski, Tobias
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    Nießing, Bastian
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    König, Niels orcid-logo
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    Schmitt, Robert H.
    Phase contrast is one of the most important microscopic methods for making visible transparent, unstained cells. Cell cultures are often cultivated in microtiter plates, consisting of several cylindrical wells. The surface tension of the culture medium forms a liquid lens within the well, causing phase contrast conditions to fail in the more curved edge areas, preventing cell observation. Adaptive phase contrast microscopy is a method to strongly increase the observable area by optically compensating for the meniscus effect. The microscope’s condenser annulus is replaced by a transmissive LCD to allow dynamic changes. A deformable, liquid-filled prism is placed in the illumination path. The prism’s surface angle is adaptively inclined to refract transmitted light so that the tangential angle of the liquid lens can be compensated. Besides the observation of the phase contrast image, a beam splitter allows to simultaneously view condenser annulus and phase ring displacement. Algorithms analyze the displacement to dynamically adjust the LCD and prism to guarantee phase contrast conditions. Experiments show a significant increase in observable area, especially for small well sizes. For 96-well-plates, more than twelve times the area can be examined under phase contrast conditions instead of standard phase contrast microscopy.
  • Publication
    LIFTOSCOPE: development of an automated AI-based module for time-effective and contactless analysis and isolation of cells in microtiter plates
    ( 2023-02-07)
    Narrog, Florian orcid-logo
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    Lensing, Richard
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    Piotrowski, Tobias
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    Nottrodt, Nadine
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    Wehner, Martin
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    Nießing, Bastian
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    König, Niels orcid-logo
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    Gillner, Arnold
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    Schmitt, Robert H.
    Background: The cultivation, analysis, and isolation of single cells or cell cultures are fundamental to modern biological and medical processes. The novel LIFTOSCOPE technology aims to integrate analysis and isolation into one versatile, fully automated device. Methods: LIFTOSCOPE’s three core technologies are high-speed microscopy for rapid full-surface imaging of cell culture vessels, AI-based semantic segmentation of microscope images for localization and evaluation of cells, and laser-induced forward transfer (LIFT) for contact-free isolation of cells and cell clusters. LIFT transfers cells from a standard microtiter plate (MTP) across an air gap to a receiver plate, from where they can be further cultivated. The LIFT laser is integrated into the optical path of an inverse microscope, allowing to switch quickly between microscopic observation and cell transfer. Results: Tests of the individual process steps prove the feasibility of the concept. A prototype setup shows the compatibility of the microscope stage with the LIFT laser. A specifically designed MTP adapter to hold a receiver plate has been designed and successfully used for material transfers. A suitable AI algorithm has been found for cell selection. Conclusion: LIFTOSCOPE speeds up cell cultivation and analysis with a target process time of 10 minutes, which can be achieved if the cell transfer is sped up using a more efficient path-finding algorithm. Some challenges remain, like finding a suitable cell transfer medium. Significance: The LIFTOSCOPE system can be used to extend existing cell cultivation systems and microscopes for fully automated biotechnological applications.
  • Publication
    High-Speed-Microscopy for Scalable Quality Control in Automated Production of Stem Cell Spheroids for Tissue Engineering
    ( 2023)
    Krieger, Judith
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    Nießing, Bastian
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    König, Niels orcid-logo
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    Schmitt, Robert
    The EU Horizon 2020 project »JointPromise« implies the conception and implementation of an end-to-end automated production platform for three-dimensional joint implants, paving the way for tissue-engineered implants able to regenerate deep osteochondral defects. Spheroid-based implants provide a novel approach in tissue engineering by aggregating progenitor cells into potent microtissues. After the differentiation of cartilaginous microtissues, functional joint implants are assembled via 3D bioprinting to match the complex structural organization of native cartilage tissue. As the automation approach of the project aims to overcome bottlenecks in manual production such as product variability, lack of scalability and high personnel costs, a high-throughput quality control system is crucial for the production of reliable Advanced Therapy Medicinal Products (ATMPs). By establishing not only a technical solution for the full digitization of the cell culture plates but also an intelligent image processing algorithm for the detection of the cell spheroids, relevant process parameters like size distribution and growth curves can be detected. Critical thresholds in spheroid growth are evaluated to minimize risks of carcinogenic tissue formation in vivo as well as to define harvest criteria to prevent inhomogeneous bioprinting results. In order to calculate the required throughput and elaborate optimization potentials of the automated spheroid production, voids in the cultivation vessel or disrupted aggregates due to media changes or transportation are detected. Ultimately, the high-speed-microscopy complies with the requirements of a high-throughput automated cell production platform to meet the rising demand for alternative therapeutic approaches in regenerative medicine.
  • Publication
    Effiziente Analytik in Labor und Produktion
    ( 2022)
    Janning, Kai
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    Nießing, Bastian
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    König, Niels orcid-logo
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    Schmitt, Robert H.
    Um Mikroskopie für Analytik und Qualitätskontrollen im Labor effizient zu automatisieren, sind eine schnelle Digitalisierung der Proben und eine parallele Bildauswertung erforderlich. Moderne High-Speed-Mikroskope vereinen hohe Aufnahmegeschwindigkeiten mit intelligenter Software für individuelle Auswertungen. Vor allem bei der Herstellung von Arzneimitteln für neue Therapien liefert dies einen großen Mehrwert.
  • Publication
    Smarte Steuerung flexibler Produktionssysteme. Ein service-orientierter Ansatz zur Automatisierung adaptiver, individueller Prozesse
    ( 2020)
    Hort, Simon orcid-logo
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    Nießing, Bastian
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    Jung, Sven
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    Schmitt, Robert H.
    Um trotz kleiner Stückzahlen kundenindividuelle Produkte effizient herstellen zu können, müssen Produktionssysteme variable Prozesse ausführen und Aufträge optimal einsteuern können. Bei der Umsetzung birgt - neben einer variablen Verkettung der Maschinen - die steuerungsseitige Implementierung große Herausforderungen. Dieser Beitrag stellt sich letzterer Herausforderung und zeigt einen service-orientierten Ansatz zur intelligenten, adaptiven Prozesssteuerung auf.