Development of microreactor technology for enzymatic processes and application for lactose conversion

The vision for this project is to achieve accelerated design of industrially relevant bioprocesses by overcoming known bottlenecks in the overall development scheme using microreactor technology. The planned project is concerned with the widely recognized problem that implementation of novel bioprocesses in industry is often severly hampered because main goals along the development train are not realized in a timely fashion and with full retention of process productivity and product quality. There is a clear need for automated methods with high-throughput capacity that

1. can be used in the selection and optimization of the biocatalyst under the operational conditions, and
2. assist in the transfer of the process from laboratory to pilot or production scales.

The results of this project will offer innovative solutions for these key difficulties of bioprocess development by fulfilling two major aims, which follow.

The first goal is building up a novel type of a microliter-scale reactor which can be applied in a very flexible manner to a range of enzyme-catalyzed biotransformation. This reactor will consist of one or more units of microstructured reaction plates which are assembled into a metal housing that will have the approximate size of a matchbox. The reaction plates will be made of glass or silicon, and their surfaces will display an array of microfluidic channels of about 100 µm diameter. The microstructure of the plate is made by high-precision microfabrication such as wet etching, for example, and will be optimized for enzyme immobilization. The enzyme reactor is based on the covalent attachment of the enzymes on to the surface of the microchannels using chemical coupling procedures. Using this type of reactor in multi-plate configuration under conditions of continuous operation, automated screening of different enzymes and of various reaction conditions is made possible. Another key advantage of the microdevice is that scale up is simply achieved through a parallel or serial combination of the number of units required to process a certain volume of substrate (numbering up). By contrast, scale up in conventional process technology is labour-intensive and often unpredictable (thus risky) because theory is extremely complicated and not fully developed. A probably large benefit of microreactor technology applied to enzyme-catalyzed processes lies in the fact that the physical transport of mass and heat is greatly (> 10-fold) enhanced at the microscale mainly because a very large surface-to-volume ratio is achieved in the small systems. Elimination of kinetic limitations due to mass transfer and improved mixing at the microscale are essential components which guarantee that the immobilized enzyme activity is utilized as completely as possible. The model technology developed in the project will be of interest to both researchers in academia and industry, and process engineers. Clearly, to solve fundamental problems of the technology, we need to use a model enzyme, ideally one of industrial relevance, that is well characterized. Here, lactases are chosen which are enzymes that hydrolyze lactose into the constituent monosaccharides glucose and galactose.

The second goal of the project is the application of the new technology for the enzymatic conversion of lactose in cheese whey. The aim is to provide the basis for the realization of an industrial process based on microreactor technology. Whey accumulates in very large amounts Europe-wide and within the region as result of cheese production. Whey is recognized to be a potentially valuable raw material. However, new and better uses for it must be developed in order to prevent that a large portion of the annual production figure is disposed of, thereby contaminating industrial waste water streams and causing environmental problems. Lactose is the main carbohydrate in whey. Its hydrolysis helps to enhance the bioavailability of the sugar for uses in food and feed; improves further processing of the raw material into whey-derived products because crystallisation of lactose is prevented; and generally contributes to added value. The project plan is to increase the productivity of the enzymatic hydrolysis process by using microreactor technology; and transfer results from the lab bench to the pilot or industrial scale using the concept of numbering-up (replication of units). Therefore, the project contributes to the establishment of an efficient and sustainable model process of high potential for innovation.

Project management

o.Univ.-Prof. Dr. Bernd Nidetzky
Institut für Bioprozesstechnik und Biotechnologie der TU Graz

Project- and cooperation partners

• VTU Engineering Planungs- und Beratungsgesellschaft mbH
  Parkring 18, A-8074 Grambach/Graz
  E-Mail: michael.koncar@vtu.com
• Hämosan Lifescience Services GmbH
  Neudorf 41, A8262 Ilz
  E-Mail: herwig.reichl@haemosan.com
• Microinnova Engineering GmbH
  Reininghausstraße 13a, 8020 Graz
  E-Mail: dirk.kirschneck@microinnova.com

Angewandte Biokatalyse Kompetenzzentrum GmbH
Institut für Bioprozesstechnik und Biotechnologie der TU Graz
o.Univ.-Prof. Dr. Bernd Nidetzky
Petersgasse 12, A-8010 Graz
Tel.: +43 (316) 873 8400
E-Mail: bernd.nidetzky@a-b.at