Activities at the Biotechnology unit
Our research and education focus on industrial applications in biotechnology. The scientific breakthroughs during the past decades in molecular biology have unfolded exceptional developments for realisation of industrial products such as biopharmaceuticals, therapeutic cells, biosensors and DNA microarrays. At IFM we dedicate much of our research to engineering design of biotechnology systems with the purpose to enhance efficient production of biologics and fabrication of devices. A few examples follow below:
- Design of cell-based assays: To develop safe, efficient and competitive new medicines remain very demanding and require substantial time in the biopharmaceutical industry. Our ambition is to contribute to shorten the development time by inventing new cell-based assays with higher accuracy and speed at lower cost per analysis. In recent years we have actively exploited pluripotent stem cells and advanced sensor methods for developing better assay methodology for safety and efficacy testing. This has included development of new cell-based assays for cardiac and liver cells, together with partners in EU-projects:
- Christoffersson J, Meier F, Kempf H, Schwanke K, Coffee M, Beilmann M, Zweigerdt R, Mandenius CF (2018) A cardiac cell outgrowth assay for evaluating drug compounds using a cardiac spheroid-on-a-chip device. Bioengineering 5, 36.
- Cader Z, Graf M, Burcin M, Mandenius CF, Ross J, (2019). Cell-based assays using differentiated human induced pluripotent cells. In Mandenius and Ross (eds.), Cell-Based Assays Using iPSCs for Drug Development and Testing, Methods in Molecular Biology, vol. 1994, 1-14, Springer Nature
Bioprocess monitoring and control by novel sensors: The biotechnology industry lacks real-time sensors for critical quality parameters. We develop methods based on soft sensors to accomplish online monitoring, modelling, and control of bioprocesses with the purpose to enhance better product quality, higher productivity, and more sustainable processes, in compliance with the Process Analytical Technology (PAT) principles.
- Mandenius CF, Gustavsson R (2016) Soft sensor design for bioreactor monitoring and control. In: Bioreactors: Design, Operation and Novel Applications (Editor C.F. Mandenius) Wiley VCH, Weinheim, Germany.
- Randek J, Mandenius CF (2018) On-line soft sensing in upstream bioprocessing. Critical Review Biotechnology 38, 106-121.
- Greuel S, Freyer N, Hanci G, Böhme M, Miki T, Werner J, Schubert F, Sittinger M, Zeilinger K, Mandenius CF (2019). Online measurement of oxygen enables continuous non-invasive evaluation of human induced pluripotent stem cell (hiPSC) culture development in a perfused 3D hollow fiber bioreactor. J. Tissue Eng. Regen. Med. 13(7), 1203-1216.
- Mandenius CF (2021) Measurement Technologies for Upstream and Downstream Bioprocessing, MDPI Books, Basel, Switzerland https://doi.org/10.3390/books978-3-0365-1151-1
Microfluidics and organ-on-chips: Organ-on-a-Chip and microfluidics are by FDA and other regulatory organisations examples of microphysiological systems with high potential for providing more relevant and accurate disease and drug models. Our main ambition is to provide small micro-designed systems with stem cell-derived organ cells.
- Bergström G, Christoffersson J, Zweigerdt R, Schwanke K, Mandenius CF (2015) Stem cell derived cardiac bodies in a microfluidic device for toxicity testing by beating frequency imaging. Lab Chip 15, 3242-3249.
- Pasitka L, van Noort D, Lim W, Park S, Mandenius CF (2018). A microbore tubing-based spiral for multi-step cell fractionation. Anal Chem 90, 21, 12909-12916.
- Christoffersson J, Mandenius CF (2019) Using a microfluidic device for culture and drug toxicity testing of 3D cells. In Mandenius and Ross (eds.), Cell-Based Assays Using iPSCs for Drug Development and Testing, Methods in Molecular Biology, vol. 1994, 235-241, Springer Nature.
Conceptual design for biotechnology applications: The biotechnology industry can speed up its development of new products and processes by applying systematic and efficient engineering design methodology. We use a conceptual and functional thinking in the design process before we start resource-demanding prototyping and construction work.
- Mandenius CF, Björkman M (2011) Biomechatronic design in biotechnology: A methodology for development of biotechnology products. Wiley & Sons, Inc., Hoboken, New Jersey, USA.
- Christoffersson J, van Noort D, Mandenius CF (2017) Developing organ-on-a-chip concepts using bio-mechatronic design methodology. Conceptual design of an Organ-on-a-Chip. Biofabrication 9, 025023.
- Mandenius CF (2021) Realization of user-friendly bioanalytical tools to quantify and monitor critical components in bio-industrial processes through conceptual design. Engineering in Life Science 2021:1–12 https://doi.org/10.1002/elsc.202100116