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Practical report: the combination of biology and process engineering

If the environment is right and both sides are genuinely interested in working together, then the cooperation between biologists and engineers will lead to top technologies. One example of such cooperations is the bioreactors of the Department of Cell Systems at the Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB in Stuttgart.

At first, there were many wow effects, on both sides, recalls Professor Dr. Heike Mertsching, head of the Department of Cell Systems at the IGB. Although this no longer happens very often, the IGB’s biologists and engineers who are working on the development of bioreactors still have to discuss and explain very specific issues amongst themselves, explains Mertsching alluding to some of the problems that arise when biologists and engineers decide to join forces. Mertsching referred to an example that led to some confusion right at the beginning of the cooperative project: “If biologists refer to a matrix, then they have the carrier material for tissue in the bioreactors in mind. However, for engineers, matrices are mathematical structures used to develop processes. The scientists were talking at cross purposes without even realising.”

Terminology obstacles are not the only ones that make the combination of the biological and engineering sciences difficult. The approaches are often very different. Mertsching: “For example, the engineers asked for standard conditions and specifications giving details on the required functions of devices, the underlying parameters and the deviations that can be tolerated. We biologists are not used to such requirement specifications.” Nevertheless, Mertsching finds the permanent exposure to different ways of thinking and research structures as very enriching, in particular as, in her experience, this has led to effective cooperation.
Two scientists in discussion in front of a computer workstation
Computer-assisted bioreactor system at the Fraunhofer IGB can be used to simulate the blood flow through a human organ under physiological conditions. (Photo: Prof. Dr. Heike Mertsching, Fraunhofer IGB)

Mutual benefit has priority

“Biotechnology benefits process engineering and vice versa,” said Mertsching. The success of her own projects seems to confirm this. When the cell specialist moved from the medical faculty at the University of Hanover to Stuttgart, a major reason for doing so was the excellent process engineering environment at the IGB and at the University of Stuttgart. “Our biological methods were mature enough to be turned into technological applications. I was convinced that the more technical environmental in Stuttgart was better than the medical environment in Hanover if I wanted to achieve this goal,” said Mertsching.
Be it trachea, intestines or liver – all three 3D models developed at the IGB are based on the same module, which has been further developed for each specific application area. The bioreactor is basically an incubator in which cultivated tissue is provided with media via a computer. In order to be able to simulate the situation in the organism as authentically as possible, the tissue has to be vascularised, i.e. have vessels that enable the exchange of nutrients and active substances with the media. This was one of the greatest challenges for Mertsching’s interdisciplinary team.

Development of bioreactors requires interdisciplinary support

The liver reactor has progressed enormously and a test system is now available that can be used to test the effect of drugs on humans. “Tissue cultivation has been standardised to a degree that enables us to produce similar tissue in about three weeks. In addition, the software has become really sophisticated and enables us to simulate cardiac arrythmia or high blood pressure,” explained Mertsching who is soon hoping to be able to simulate even more complex physiological conditions such as stress phases in patients in order to examine how the effect of drugs changes.
Photograph of the Fraunhofer IGB bioreactor.
The Fraunhofer IGB bioreactors are major components of vascularised in vitro test systems. (Photo: Prof. Dr. Heike Mertsching, Fraunhofer IGB)
At present, the bioreactors are being validated, a task which also involves interdisciplinary teams. “At first, we have to find out what can be validated and which statements hold water. An important issue is to examine how our results correlate with in vivo situations,” said Mertsching who is hoping to take the current state of process engineering an important step further forward, namely towards automation. She is hoping to automate the system to the extent that it will be possible to perform automatic drug tests. In order to achieve this, Mertsching’s team is working in close cooperation with the IPA, the Fraunhofer Institute for Manufacturing Engineering and Automation, which is also based in Stuttgart.

Automation throws up entirely new challenges. “The engineers told us that they required a material flow analysis, something we biologists had not dealt with before. Put simply, in the field of biology, we just put a biopsy into an incubator and took out the tissue,” said Mertsching who once again benefits from the technical approach. “We are being encouraged to deal with things on a physical level, and we get the chance to optimise the processes so that the natural variability of any biological system is diminished.”

Biological variability can be reduced but must also be tolerated

Mertsching refers to a simple but impressive example of how biological methods can be improved with process engineering: “In order to isolate skin cells from a sample, we used to take a pair of tweezers to carefully separate the individual skin layers from one another and then remove individual cells. It is difficult to automate such a method. However, process engineering helped us to establish a physical method in which the tissue is fragmented and the cells are separated according to their physical properties such as size and weight. This method of creating individual cells is a lot quicker than our previous method. Currently, we are carrying out analyses to make sure that the cells are not damaged more than with the other method.”

Engineering concepts are thus revolutionising the work of biologists and confirm bioprocess engineering as a model of success in a new field of science. Classical process engineering itself also benefits from this type of cooperation. Technicians and engineers are expanding their areas and learning to tolerate a certain variability, something that is absolutely necessary when dealing with living systems. “They regard it as a kind of enrichment, in particular since exciting new aspects are appearing in their area of research. The will to approach and learn from each other is present and this is the most important thing when working to advance research and development,” said Mertsching summarising the benefit of engineers and biologists working together.

Together with colleagues from the entire region, the universities of Stuttgart and Tübingen as well as colleagues in industry, Mertsching is hoping to further advance bioprocess engineering. She is certain that an own technology centre would considerably accelerate the achievement of new insights and the development of seminal products. The prerequisites for this happening are already in place and initial contacts with the state of Baden-Württemberg have been made.

leh - 24.03.2008
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