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Project Nixes Multi-Step Chemical Processes

Aug. 15, 2017
Nature-inspired method aims to combine production stages to reduce waste

Research at the University of Bielefeld, Bielefeld, Germany, aims to do away with multi-step chemical processes and the cost, engineering complexity and waste that goes with their associated isolation and purification stages.

The Bielefeld work, led by Harald Gröger from the Center for Biotechnology (CeBiTec), is part of the €3.9-million ($4.6-million) European Union (EU)-funded One-Flow project, coordinated by the Eindhoven University of Technology, the Netherlands.

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“Because of the many stages in production, the current batch reactor-type vessel technology is particularly time consuming. A further disadvantage is that workup and isolation of intermediates lead to many waste products. Hence, the technology does not use raw materials efficiently,” explains Gröger.

After every stage in production, the intermediate typically is purified. This might require significant amounts of solvent that then become waste products, he adds.

The Bielefeld researchers are using their €400,000 ($473,000) share of the EU money on an alternative strategy known as the flow method. This combines the production stages and proceeds in microreactors that produce the desired substance without intermediate isolations.

“The flow method offers a way to reduce resource requirements and save waste, thus making production not only economically more attractive but also more sustainable,” says Gröger.

The inspiration for the flow method comes from nature. In biological cells, chemical processes proceed concurrently as so-called “domino reactions” — and they do this continuously. The conditions in cells always remain the same: the pressure, temperature, and solvent (water). In the cells, enzymes ensure the reactions are initiated and concluded.

“We want to apply the principles of the cell to production in microreactors,” notes Gröger.

Another advantage is that the new method requires far less energy and space than conventional production. The microreactors mostly use plug-flow reactors with flow tubes with an average diameter of “much less than one millimeter.”

“What’s special is that we can also produce large amounts of material on a small scale. This enables us to gain the substance at a specifically desired amount without great effort. If we want to increase the amount, we simply add extra microreactors. Hence, problems with upscaling disappear,” explains Gröger.

Before this can happen, the team must overcome a number of obstacles. An important one is working out how to conduct several reactions concurrently in the miniaturized flow tube in a way that stops them interfering with each other. “We are developing methods that will ensure that each reaction is shielded,” Gröger notes.

Another is ensuring catalysts used to initiate reactions not only perform at their peak under the chosen reaction conditions, but also return to their initial state at the end of the process and so can be used repeatedly.

Here, Gröger’s team is relying on its existing research knowledge on combining bio- and chemo-catalysts. “In nature, bio-catalysts are found in the form of enzymes. Chemo-catalysts, in contrast, are developed artificially. By combining chemo- and bio-catalysts in a flow reactor, we want to efficiently produce pharmaceutically relevant products at room temperature and thereby produce them in a more sustainable and specific mode,” says Gröger.

The EU rated One-Flow, a four-year project launched at the beginning of 2017, 12th out of more than 500 research proposals of which only 23 received funding.

What particularly attracted EU research funders is the way One-Flow translates the vertical hierarchy of chemical multistep synthesis with its complex machinery into self-organizing horizontal hierarchy of a compartmentalized flow reactor system — a biomimetic digital flow cascade machinery with just one reactor passage. “To keep horizontal hierarchy manageable, orthogonality among the consecutive reactions needs to be increased. The winning point of nature is to have invented catalytic cascades. One-Flow will uplift that by enabling the best bio- and chemo-catalysts working hand in hand,” notes the project description.

Further, the EU believes One-Flow has massive impact potential, including a €38-billion ($45-billion) saving in overall production costs; a €300-million ($355-million) savings during drug development; better addressing diseases that have so far cost the EU €500 billion ($591 billion) in medication costs; increasing market share of emerging high-tech small- and medium-size players by 10% in 10 years; and opening windows of opportunity, for example in personalized medicine.

Eindhoven University of Technology and Bielefeld University are cooperating on the project with Delft University of Technology, the Netherlands; Graz University of Technology, Austria; the National Center for Scientific Research, Paris, France; the universities of Cambridge and Hull, U.K.; and process intensification company Microinnova Engineering, Allerheiligen bei Wildon, Austria.

Seán Ottewell is Chemical Processing's Editor at Large. You can email him at [email protected].

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