Projects

Numerous valuable compounds, so-called secondary metabolites, are produced by plant cells, typically by the collaboration of different and specialized cell types. However, many of these complex compounds cannot be produced through chemical synthesis. As a result, these secondary metabolites have to be extracted directly from plants. As some plants are rare or endangered species, the biotechnological production of these complex compounds is of high interest. Nevertheless, the conditions in batch fermenters lead to a suppression of the differentiation of plant cells and harvesting of secondary metabolites. Thus, there is a high motive force in developing a new process for an in-vitro production.

As a technical solution, different cell types are integrated in several modular microfluidic bioreactors, which are linked with a metabolic flow and mimic a natural connection of different plant tissues. This microfluidic bioreactor consists of two chambers, which are separated by a permeable membrane (Fig. 1). In the upper chamber, the cells are inserted and cultivated. The lower chamber is perfused by a nutrient solution. The porous membrane enables the supply with nutrient solution from the lower chamber while retaining the cells in the upper chamber. In addition, the secondary metabolites from the cells can be exchanged through the membrane. Moreover, the transparency and the low thickness of the upper chamber provide live cell imaging and monitoring of cell processes (Fig. 2).

Figure 1: Schematic cross section of the modular microfluidic bioreactor: The cell chamber (green)
is filled with cells from above and closed with plugs, the nutrient solution (blue) flows from below.
Both chambers are separated by a permeable membrane (red).

Regarding low-cost production, the two chamber parts of the microfluidic bioreactor are replicated by hot embossing and assembled with commercial available permeable membranes by ultrasonic welding. Ultrasonic welding represents a connection technology which generates the required tight, stable and - most important - biocompatible joint without any support of adhesive.

At the welding process, the ultrasonic energy generates molecular and interfacial friction between the joint partners. Thus, heat is created that plasticizes the material. So-called energy directors, which belong to the structure of at least one joint partner, support a local and specific welding. The whole welding process takes less than 1 s and after cooling, the joint partners are irreversibly bonded by a homogeneous welding seam. With this technique, fluidic connections can be integrated, too - out of plane as well as in plane.

  

Figure 2: Cell processes can be monitored under the microscope due to the chip design and its transparency.

 Dr. Ralf Ahrens [Contact]