Dipl.-Phys.

König, Niels

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  • Publication
    Young’s Modulus-Independent Determination of Fibre Parameters for Rayleigh-Based Optical Frequency Domain Reflectometry from Cryogenic Temperatures up to 353 K
    ( 2023-05-09)
    Girmen, Caroline
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    Dittmar, Clemens
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    Siedenburg, Thorsten
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    Gastens, Markus
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    Wlochal, Michael
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    König, Niels orcid-logo
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    Schröder, Kai-Uwe
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    Schael, Stefan
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    Schmitt, Robert H.
    The magnetic spectrometer AMS-100, which includes a superconducting coil, is designed to measure cosmic rays and detect cosmic antimatter in space. This extreme environment requires a suitable sensing solution to monitor critical changes in the structure such as the beginning of a quench in the superconducting coil. Rayleigh-scattering-based distributed optical fibre sensors (DOFS) fulfil the high requirements for these extreme conditions but require precise calibration of the temperature and strain coefficients of the optical fibre. Therefore, the fibre-dependent strain and temperature coefficients 𝐾T and 𝐾𝜖 for the temperature range from 77 K to 353 K were investigated in this study. The fibre was integrated into an aluminium tensile test sample with well-calibrated strain gauges to determine the fibre’s 𝐾𝜖 independently of its Young’s modulus. Simulations were used to validate that the strain caused by changes in temperature or mechanical conditions was the same in the optical fibre as in the aluminium test sample. The results indicated a linear temperature dependence of 𝐾𝜖 and a non-linear temperature dependence of 𝐾T. With the parameters presented in this work, it was possible to accurately determine the strain or temperature of an aluminium structure over the entire temperature range from 77 K to 353 K using the DOFS.
  • 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
    5G-Sierra: Secure 5G infrastructures for resilient production systems and facilities
    ( 2022-11-28)
    Brochhaus, Maximilian
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    Kehl, Pierre orcid-logo
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    König, Niels orcid-logo
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    Kreppein, Alexander
    Networking of industrial production systems using 5G poses some technical hurdles and risks.
  • 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
    5G-Industry Campus Europe
    (Fraunhofer IPT, 2022)
    König, Niels orcid-logo
    ;
    Kehl, Pierre orcid-logo
    The 5G-Industry Campus Europe offers a unique ecosystem for research, development and testing of 5G technology for industrial applications. The Fraunhofer IPT and its research partners in Aachen are testing the first industrial 5G applications at the 5G-Industry Campus Europe. In seven sub-projects, various application scenarios are being researched, from 5G sensor technology for monitoring and controlling complex manufacturing processes, mobile robots cooperating on an assembly task, or AGVs (automated guided vehicles) enabling flexible and logical supply chains - for all these applications, 5G offers the possibility of reliable real-time communication and thus the possibility of networked, adaptive production. Furthermore, the research partners are also testing the use of modern edge cloud systems for fast data processing in order to exploit the potential of 5G in networked, adaptive production.
  • Publication
    Needle to needle robot‐assisted manufacture of cell therapy products
    ( 2022)
    Ochs, Jelena
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    Hanga, Mariana P.
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    Shaw, Georgina
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    Duffy, Niamh
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    Kulik, Michael
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    Tissin, Nokilaj
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    Reibert, Daniel
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    Biermann, Ferdinand
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    Moutsatsou, Panagiota
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    Ratnayake, Shibani
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    Nienow, Alvin
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    König, Niels orcid-logo
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    Schmitt, Robert
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    Rafiq, Qasim
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    Hewitt, Christopher J.
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    Barry, Frank
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    Murphy, J. Mary
    Advanced therapeutic medicinal products (ATMPs) have emerged as novel therapiesfor untreatable diseases, generating the need for large volumes of high-quality,clinically-compliant GMP cells to replace costly, high-risk and limited scale manualexpansion processes. We present the design of a fully automated, robot-assistedplatform incorporating the use of multiliter stirred tank bioreactors for scalable pro-duction of adherent human stem cells. The design addresses a needle-to-needleclosed process incorporating automated bone marrow collection, cell isolation,expansion, and collection into cryovials for patient delivery. AUTOSTEM, a modular,adaptable, fully closed system ensures no direct operator interaction with biologicalmaterial; all commands are performed through a graphic interface. Seeding of sourcematerial, process monitoring, feeding, sampling, harvesting and cryopreservation areautomated within the closed platform, comprising two clean room levels enablingboth open and closed processes. A bioprocess based on human MSCs expanded onmicrocarriers was used for proof of concept. Utilizing equivalent culture parameters,the AUTOSTEM robot-assisted platform successfully performed cell expansion at theliter scale, generating results comparable to manual production, while maintaining cellquality postprocessing.
  • Publication
    Skalierbare Herstellung von ATMPs
    ( 2022)
    Gebken, Natalie
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    Horbelt, Jessica
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    Kleine-Wechelmann, Sarah
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    Ort, Thomas
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    Puls, Sebastian
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    Schandar, Markus
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    Traube, Andreas
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    Biermann, Ferdinand
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    Brandstätter, Tobias Claus
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    Gräfe, Stefan
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    Herbst, Laura
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    König, Niels orcid-logo
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    Schmitt, Robert
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    Ackermann, Heiner
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    Diessel, Erik
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    Lengen, Rolf Hendrik van
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    Schmidt, Andreas
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    Braun, Dennis
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    Hunger, Sandra
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    Werner, Michael
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    Boskovic, Dusan
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    Mendl, Alexander
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    Graumann, Tobias
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    Lachmann, Kristina
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    Mann, Annika
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    Brehmer, Annika
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    Dürre, Gregor
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    Hein, Christoph
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    Blache, Ulrich
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    Dluczek, Sarah
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    Dünkel, Anna
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    Franz, Paul
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    Fricke, Stephan
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    Tradler, Thomas
    Die Entwicklung von Arzneimitteln für neuartige Therapien (ATMPs; Advanced Therapy Medicinal Products) schreitet schnell voran. Erste Produkte haben bereits die Marktzulassung erhalten und sind kommerziell erhältlich. Ihre Produktion ist jedoch von komplexen manuellen Abläufen, hochspezialisierten Geräten und den damit verbundenen hohen Produktionskosten geprägt. Aufgrund der Neuartigkeit und der hohen Komplexität bei der Produktion kann das volle klinische Potential von ATMPs in Zukunft unter den bestehenden Produktionsbedingungen nicht ausgeschöpft werden. Darüber hinaus nehmen die am Markt zugelassenen Produkte und die klinischen Anwendungsgebiete von ATMPs stetig zu, was langfristig nicht nur zu einem Engpass in der Produktion, sondern auch zu einer hohen finanziellen Belastung des Gesundheitssystems führen wird. Um die Herstellkosten von ATMPs zu senken und sie vielen Patientinnen und Patienten zur Verfügung stellen zu können, sind neue Konzepte entlang der gesamten Wertschöpfungskette erforderlich. Dafür muss die Produktion insbesondere stärker automatisiert und digitalisiert werden. Unterschiedliche Konzepte sind hier vielversprechend für eine vollautomatisierte Produktion, im Sinne einer vollintegrierten Automatisierung oder eines modularen Aufbaus der Produktionsumgebung. Die Implementierung dieser Konzepte setzt neue Entwicklungen voraus, von der Entnahme der Zellen bei der Spenderin oder beim Spender über die Produktionstechnologien an sich bis hin zur finalen Formulierung und Abfüllung des Produkts. Neben Änderungen im Bereich der Hardware werden auch neue Softwarelösungen notwendig, beispielsweise zur Planung und Auswahl geeigneter Produktionsszenarien. Auch für die eigentliche Produktion von ATMPs und die damit verbundenen Daten müssen zukünftig neue Technologien, wie bspw. integrierte Prozesskontrollen, die Prozessbegleitung mittels Digitalem Zwilling oder die Analyse sowie Prozesssteuerung mittels Künstlicher Intelligenz (KI) berücksichtigt werden, um das volle Automatisierungspotential ausschöpfen zu können.