Microfluidic in vitro lung model for the replacement of murine infection and Acute Respiratory Distress Syndrome (ARDS) models

PD Dr. Christoph Beißwenger,
Universität des Saarlandes, Homburg/Saar

Prof. Dr. Heiko Zimmermann,
Fraunhofer-Institut für Biomedizinische Technik, Sulzbach


Microfluidic in vitro lung models can help to reduce and replace the need for animal studies in drug development and in basic research.

Inflammatory cells (e.g. neutrophils) contribute to the loss of lung structure and lung function in lung diseases, such as pneumonia, acute respiratory distress syndrome (ARDS), and cystic fibrosis. This project aimed to cultivate human endothelial and epithelial cells and the development of a microfluidic chip system, which allows to examine transepithelial migration of neutrophil granulocytes from the blood stream into the lung.

The microfluidic chip was realized in microscope slide size (fig. 1).


Fig. 1:  
Microfluidic chip system for cell cultivation and measurement of transepithelial migration of neutrophil granulocytes. The chip has integrated gold electrodes to measure the impedance.


Human epithelial cells from the respiratory tract were cultivated in the microfluidic system. Quantification of cell growth and cell densitiy was performed by impedance measurement (fig 2A). In order to test for migration of neutrophiles over the epithelial barrier neutrohile granulocytes were placed into the bottom channel. To stimulate the migration heat inactivated cells of the pathogen Pseudomonas aeruginosa were added to the liquid flowing in the upper channel. Migration of neutrophiles has been confirmed (fig. 2B).

Fig. 2:   Examination of neutrophil migration across the epithelium of the respiratory tract.
(A) Time dependent course of impedance during cell cultivation in the microchip. (B) Number of migrated cells, which crossed the epithelial barrier.


In another part of this project primary human bronchial epithelial cells were differentiated to bronchospheres during a time span of four to five weeks. These bronchospheres can be used to examine the interaction of epithelial cells with inflammatory cells like neutrophils. During differentiation the bronchospheres were incubated with bacterial factors like flagellins from P. aeruginosa, leading to mucus hyperproduction.

Microfluidic in vitro models and lung organoids can be used to analyse the interaction of inflammatory cells with bronchial epithelial cells under physiological conditions. The newly developed models follow the 3Rs principles and contribute to the reduction of animal experiments in the field of drug development and basic research.


Sprott et al. (2020) Flagellin shifts 3D bronchospheres towards mucus hyperproduction. Respiratory Research 21:222; doi.org/10.1186/s12931-020-01486-x

Hesler M., Knoll T., Ritzmann F., Honecker A., Wagner S., Kohl Y., von Briesen H., Zimmermann H., Bals R., Beisswenger C. „Microfluidic in vitro lung model to replace murine infection and ARDS models“ Posterpräsentation während der EUSAAT, 10.-13. Oktober 2019, Linz, Österreich.



Universität des Saarlandes - Innere Medizin V
Geb. 61.4, 66421 Homburg/Saar

Fraunhofer-Institut für Biomedizinische Technik IBMT
Joseph-von-Fraunhofer-Weg 1, 66280 Sulzbach


03/2018 - 08/2019