Biotechnology

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:

Publications:

  • 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.

Publications:

  • 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.

Publications:

  • 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.

Publications:

  • 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

Contact

Education

Publications

2020

Christopher Aronsson, Michael Jury, Sajjad Naeimipour, Fatemeh Rasti Boroojeni, Jonas Christoffersson, Philip Lifwergren, Carl-Fredrik Mandenius, Robert Selegård, Daniel Aili (2020) Dynamic peptide-folding mediated biofunctionalization and modulation of hydrogels for 4D bioprinting Biofabrication, Vol. 12, Article 035031 (Article in journal) Continue to DOI
Yonghee Kim, Abdurhaman Teyib Abafogi, Buu Minh Tran, Jaewon Kim, Jinyeop Lee, Zhenzhong Chen, Pan Kee Bae, Kyoungsook Park, Yong-Beom Shin, Danny van Noort, Nae Yoon Lee, Sungsu Park (2020) Integrated Microfluidic Preconcentration and Nucleic Amplification System for Detection of Influenza A Virus H1N1 in Saliva Micromachines, Vol. 11, Article 203 (Article in journal) Continue to DOI
Abdurhaman Teyib Abafogi, Jaewon Kim, Jinyeop Lee, Merem Omer Mohammed, Danny van Noort, Sungsu Park (2020) 3D-Printed Modular Microfluidic Device Enabling Preconcentrating Bacteria and Purifying Bacterial DNA in Blood for Improving the Sensitivity of Molecular Diagnostics Sensors, Vol. 20, Article 1202 (Article in journal) Continue to DOI

2019

Seung Joon Lee, Tae Seok Sim, Hyun Young Shin, Jungmin Lee, Min Young Kim, Joseph Sunoo, Jeong-Gun Lee, Kyungmoo Yea, Young Zoon Kim, Danny van Noort, Soo Kyung Park, Woon-Hae Kim, Kyun Woo Park, Minseok S Kim (2019) Microslit on a chip: A simplified filter to capture circulating tumor cells enlarged with microbeads PLOS ONE, Vol. 14, Article e0223193 (Article in journal) Continue to DOI
Hyun Young Shin, Seung Joon Lee, Hyung Woo Seo, Min Young Kim, Aseer Intisar, Kyungmoo Yea, Sung Chun Cho, Yun-Il Lee, Young Zoon Kim, Ogan Gurel, Danny van Noort, Sang Chul Park, Minseok S. Kim (2019) Cell Seeding Technology for Microarray-Based Quantitative Human Primary Skeletal Muscle Cell Analysis Analytical Chemistry, Vol. 91, p. 14214-14219 (Article in journal) Continue to DOI
Patricia Roch (2019) Monitoring of product variants in biopharmaceutical downstream processing: Mechanistic and data-driven modeling approaches
Danny van Noort (2019) Editorial for the Special Issue on Microfluidics for Cells and Other Organisms Micromachines, Vol. 10, Article 520 (Article in journal) Continue to DOI
Patricia Roch, Anton Sellberg, Niklas Andersson, Matthias Gunne, Peter Hauptmann, Bernt Nilsson, Carl-Fredrik Mandenius (2019) Model-based monitoring of industrial reversed phase chromatography to predict insulin variants Biotechnology progress (Print), Vol. 35, Article UNSP e2813 (Article in journal) Continue to DOI
Selina Greuel, Guengoer Hanci, Mike Boehme, Toshio Miki, Frank Schubert, Michael Sittinger, Carl-Fredrik Mandenius, Katrin Zeilinger, Nora Freyer (2019) Effect of inoculum density on human-induced pluripotent stem cell expansion in 3D bioreactors Cell Proliferation, Vol. 52, Article e12604 (Article in journal) Continue to DOI
Selina Greuel, Nora Freyer, Gungor Hanci, Mike Bohme, Toshio Miki, Johannes Werner, Frank Schubert, Michael Sittinger, Katrin Zeilinger, Carl-Fredrik Mandenius (2019) Online measurement of oxygen enables continuous noninvasive evaluation of human-induced pluripotent stem cell (hiPSC) culture in a perfused 3D hollow-fiber bioreactor Journal of Tissue Engineering and Regenerative Medicine, Vol. 13, p. 1203-1216 (Article in journal) Continue to DOI
Robert Gustavsson, Carl-Fredrik Mandenius, S. Löfgren, T. Scheper, P. Lindner (2019) In situ microscopy as online tool for detecting microbial contaminations in cell culture Journal of Biotechnology, Vol. 296, p. 53-60 (Article in journal) Continue to DOI
Jonas Christoffersson, Christopher Aronsson, Michael Jury, Robert Selegård, Daniel Aili, Carl-Fredrik Mandenius (2019) Fabrication of modular hyaluronan-PEG hydrogels to support 3D cultures of hepatocytes in a perfused liver-on-a-chip device Biofabrication, Vol. 11, p. 1-13, Article 015013 (Article in journal) Continue to DOI

2018

Carl-Fredrik Mandenius (2018) Advances in Micro-Bioreactor Design for Organ Cell Studies Bioengineering (Basel, Switzerland), Vol. 5, Article 64 (Article in journal) Continue to DOI
Yi-Chin Toh, Anju Raja, Hanry Yu, Danny van Noort (2018) A 3D Microfluidic Model to Recapitulate Cancer Cell Migration and Invasion Bioengineering (Basel, Switzerland), Vol. 5 (Article in journal) Continue to DOI
Jonas Christoffersson, Florian Meier, Henning Kempf, Kristin Schwanke, Michelle Coffee, Mario Beilmann, Robert Zweigerdt, Carl-Fredrik Mandenius (2018) A Cardiac Cell Outgrowth Assay for Evaluating Drug Compounds Using a Cardiac Spheroid-on-a-Chip Device Bioengineering, Vol. 5, p. 1-13, Article 36 (Article in journal) Continue to DOI
Laura Pasitka, Danny van Noort, Wanyoung Lim, Sungsu Park, Carl-Fredrik Mandenius (2018) A Microbore Tubing Based Spiral for Multistep Cell Fractionation Analytical Chemistry, Vol. 90, p. 12909-12916 (Article in journal) Continue to DOI
Robert Gustavsson (2018) Development of soft sensors for monitoring and control of bioprocesses
Taehoon H. Kim, Young Ki Hahn, Jungmin Lee, Danny van Noort, Minseok S. Kim (2018) Solenoid Driven Pressure Valve System: Toward Versatile Fluidic Control in Paper Microfluidics Analytical Chemistry, Vol. 90, p. 2534-2541 (Article in journal) Continue to DOI
Jonas Christoffersson (2018) Organs-on-chips for the pharmaceutical development process: design perspectives and implementations
Katarina Bengtsson, Jonas Christoffersson, Carl-Fredrik Mandenius, Nathaniel D Robinson (2018) A clip-on electroosmotic pump for oscillating flow in microfluidic cell culture devices Microfluidics and Nanofluidics, Vol. 22, Article 27 (Article in journal) Continue to DOI

News about our research