M.Sc.

Nießing, Bastian

Filters

3 1
Reset filters

Settings
Now showing 1 - 10 of 27
  • 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
    ;
    Groten, Ferdinand
    ;
    Murphy, Mary
    ;
    Shaw, Georgina
    ;
    Nießing, Bastian
    ;
    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
    ;
    Aurich, Ann-Sophie
    ;
    Nießing, Bastian
    ;
    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
    Polarized Light Imaging in Life Sciences
    ( 2023-08-09)
    Nienhaus, Florian orcid-logo
    ;
    Hoffmann, Kurt
    ;
    Weltin, Louisa orcid-logo
    ;
    Nießing, Bastian
    ;
    Schmitt, Robert H.
    Polarized light imaging (PLI) is an imaging technique used to investigate the birefringent properties of samples. When examining biological samples under a microscope, the anisotropy in their interaction with light can arise from regular arrangements at either the molecular or macroscopic level. This information can be used to study the organization of fibers in connective tissues, neurons in grey and especially white matter of the brain, or to detect cancerous or abnormal tissues.
  • Publication
    Towards automated CAR-T Cell Manufacturing. Keeping up with Technological Advancement
    ( 2023-05-04)
    Herbst, Laura
    ;
    Erkens, Frederik
    ;
    Hort, Simon orcid-logo
    ;
    Bäckel, Niklas
    ;
    Nießing, Bastian
    ;
    Popp, Georg
    ;
    Franz, Paul
    ;
    König, Niels orcid-logo
    ;
    Hudecek, Michael
    ;
    Rafiq, Qasim
    ;
    Goldrick, Stephen
    ;
    Papantoniou, Ioannis
    ;
    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
    ;
    Piotrowski, Tobias
    ;
    Nießing, Bastian
    ;
    König, Niels orcid-logo
    ;
    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
    ;
    Lensing, Richard
    ;
    Piotrowski, Tobias
    ;
    Nottrodt, Nadine
    ;
    Wehner, Martin
    ;
    Nießing, Bastian
    ;
    König, Niels orcid-logo
    ;
    Gillner, Arnold
    ;
    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
    Transformative Materials to Create 3D Functional Human Tissue Models In Vitro in a Reproducible Manner
    ( 2023)
    Gerardo-Nava, José Luis
    ;
    Jansen, Jitske L.J.
    ;
    Günther, Daniel
    ;
    Klasen, Laura
    ;
    Thiebes, Anja Lena
    ;
    Nießing, Bastian
    ;
    Bergerbit, Cédric
    ;
    Meyer, Anna Astrid
    ;
    Linkhorst, John
    ;
    Barth, Mareike
    ;
    Akhyari, Payam
    ;
    Stingl, Julia Carolin
    ;
    Nagel, Saskia Kathi
    ;
    Stiehl, Thomas
    ;
    Lampert, Angelika
    ;
    Leube, Rudolf Eberhard
    ;
    Wessling, Matthias
    ;
    Santoro, Francesca
    ;
    Ingebrandt, Sven
    ;
    Jockenhoevel, Stefan
    ;
    Herrmann, Andreas
    ;
    Fischer, Horst
    ;
    Wagner, Wolfgang
    ;
    Schmitt, Robert
    ;
    Kießling, Fabian M.
    ;
    Kramann, Rafael K.
    ;
    Laporte, Laura de
    Recreating human tissues and organs in the petri dish to establish models as tools in biomedical sciences has gained momentum. These models can provide insight into mechanisms of human physiology, disease onset, and progression, and improve drug target validation, as well as the development of new medical therapeutics. Transformative materials play an important role in this evolution, as they can be programmed to direct cell behavior and fate by controlling the activity of bioactive molecules and material properties. Using nature as an inspiration, scientists are creating materials that incorporate specific biological processes observed during human organogenesis and tissue regeneration. This article presents the reader with state-of-the-art developments in the field of in vitro tissue engineering and the challenges related to the design, production, and translation of these transformative materials. Advances regarding (stem) cell sources, expansion, and differentiation, and how novel responsive materials, automated and large-scale fabrication processes, culture conditions, in situ monitoring systems, and computer simulations are required to create functional human tissue models that are relevant and efficient for drug discovery, are described. This paper illustrates how these different technologies need to converge to generate in vitro life-like human tissue models that provide a platform to answer health-based scientific questions.
  • Publication
    High-Speed-Microscopy for Scalable Quality Control in Automated Production of Stem Cell Spheroids for Tissue Engineering
    ( 2023)
    Krieger, Judith
    ;
    Nießing, Bastian
    ;
    König, Niels orcid-logo
    ;
    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
    Toward Rapid, Widely Available Autologous CAR-T Cell Therapy - Artificial Intelligence and Automation Enabling the Smart Manufacturing Hospital
    ( 2022-06-06)
    Hort, Simon orcid-logo
    ;
    Herbst, Laura
    ;
    Bäckel, Niklas
    ;
    Erkens, Frederik
    ;
    Nießing, Bastian
    ;
    Frye, Maik
    ;
    König, Niels orcid-logo
    ;
    Papantoniou, Ioannis
    ;
    Hudecek, Michael
    ;
    Jacobs, John J. L.
    ;
    Schmitt, Robert
    CAR-T cell therapy is a promising treatment for acute leukemia and lymphoma. CAR-T cell therapies take a pioneering role in autologous gene therapy with three EMA-approved products. However, the chance of clinical success remains relatively low as the applicability of CAR-T cell therapy suffers from long, labor-intensive manufacturing and a lack of comprehensive insight into the bioprocess. This leads to high manufacturing costs and limited clinical success, preventing the widespread use of CAR-T cell therapies. New manufacturing approaches are needed to lower costs to improve manufacturing capacity and shorten provision times. Semi-automated devices such as the Miltenyi Prodigy® were developed to reduce hands-on production time. However, these devices are not equipped with the process analytical technology necessary to fully characterize and control the process. An automated AI-driven CAR-T cell manufacturing platform in smart manufacturing hospitals (SMH) is being developed to address these challenges. Automation will increase the cost-effectiveness and robustness of manufacturing. Using Artificial Intelligence (AI) to interpret the data collected on the platform will provide valuable process insights and drive decisions for process optimization. The smart integration of automated CAR-T cell manufacturing platforms into hospitals enables the independent manufacture of autologous CAR-T cell products. In this perspective, we will be discussing current challenges and opportunities of the patient-specific but highly automated, AI-enabled CAR-T cell manufacturing. A first automation concept will be shown, including a system architecture based on current Industry 4.0 approaches for AI integration.