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
    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
    Techno-Economic Evaluation of 5G-NSA-NPN for Networked Control Systems
    ( 2022)
    Kiesel, Raphael
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    Schmitt, Sarah orcid-logo
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    König, Niels orcid-logo
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    Brochhaus, Maximilian
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    Vollmer, Thomas
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    Stichling, Kirstin
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    Mann, Alexander
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    Schmitt, Robert H.
    Wireless closed-loop control systems, so-called networked control systems (NCS) promise technical and economic benefits for production applications. To realize prospective benefits, the right communication technology is key. The fifth generation of mobile communication is predicted to have a significant impact on the deployment of NCS in the industrial connectivity landscape. However, there are different options for 5G deployment influencing both technical performance and economic aspects of the network. This in turn is expected to have a techno-economic influence on the production itself. Thus, a trade-off between the necessary technical performance of the 5G network and the benefits for the production must be executed. This paper, therefore, aims to analyze the techno-economic benefits of 5G deployment for closed-loop control systems in production. To reach this aim, first, the fundamentals of techno-economic analysis are introduced. Second, the results of an experimental performance analysis of a 5G-NSA-NPN at Fraunhofer IPT in Aachen are shown. Third, based on the results from the experimental study, a model-based techno-economic ex-ante evaluation of 5G-NSA-NPN for closed-loop applications is performed, and an exemplar is shown for a BLISK milling use case. Finally, the results are summarized and an outlook for further research is given. The analysis shows a difference in net present value for 5G deployment of EUR 2.6 M after 10 years and a difference of OPEX per product of around EUR -1000 per BLISK. Furthermore, analysis shows an increase in productivity (0.73%), quality (30.75%), and sustainability (2.87%). This indicates a noticeable improvement of a 5G-controlled NCS.
  • 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
    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
    Industrielle Produktionsanlagen modular erweitern mit 5G
    ( 2021)
    Schmitt, Sarah orcid-logo
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    Brunk, Nicolas
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    König, Niels orcid-logo
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    Lange, Dirk
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    Schmitt, Robert H.
    Erstmalig erhält eine Mobilfunktechnologie Einzug in die Industrie: Mit hoher Übertragungsbandbreite und geringer Latenz erfüllt 5G die Anforderungen industrieller Netzwerke und ebnet den Weg für neue Geschäftsmodelle zur Steigerung der betrieblichen Effizienz. Durch kabellose, modulare Sensorkonzepte können innovative Anwendungs-szenarien realisiert und der stetig wachsende Bedarf der Industrie nach immer flexibleren Produktionsanlagen gedeckt werden.
  • Publication
    Die Zukunft gestalten. 5G bietet neue Möglichkeiten für die Qualitätssicherung
    ( 2020)
    Schmitt, Sarah orcid-logo
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    König, Niels orcid-logo
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    Schmitt, Robert H.
    Um die großen Datenmengen in der optischen Qualitätskontrolle bewältigen zu können, sind bildverarbeitende Systeme bisher auf kabelgebundene Übertragungstechnologien eingeschränkt. Erstmalig macht ihnen eine kabellose Technologie Konkurrenz: 5G. Der neue Mobilfunkstandard kann hohe Datenmengen übertragen, bietet eine größere Reichweite und ermöglicht Echtzeitdatenauswertung in skalierbaren Cloudsystemen.
  • Publication
    Automation in the context of stem cell production - where are we heading with Industry 4.0?
    ( 2016)
    Kulik, Michael
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    Ochs, Jelena
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    König, Niels orcid-logo
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    Schmitt, Robert
    As the field of cell and gene therapy continues to progress, the need for cell products for therapeutic application is increasing. In order to meet the demands, novel challenges particularly within the manufacturing of these products need to be overcome. By translating and applying automation solutions from the production industries into cell culture applications, standardized processing procedures can be introduced in order to reduce the variability, which is a critical issue within the manufacturing workflow. Additionally, the Industry 4.0 philosophy offers a variety of concepts for the design of adaptive processes that address the specific challenges in stem cell production. Novel tools such as data tracking, data analysis and machine learning are enabling technologies that will help support the safe manufacturing of effective products for future cell and gene therapies.