Smart Reactors – Sustainable Future with Biocatalysis


-  Daniela Eixenberger, M.Sc., Institute of Technical Biocatalysis, Hamburg University of Technology -

One major focus of today’s research in industrial production is an advanced digitalization and an increasing demand of smart technology in terms of reaction design, known as “industry 4.0”. This concept is also finding significant relevance in biocatalysis, with rising trend. In fact, the majority of chemical and biochemical processes are still carried out in batch operation, predominately on an industrial scale. Optimization of reaction environments is still an underrepresented research topic, but the major focus of the program “Smart Reactors”. 

The focus of the presented research is to serve novel approaches for a rational and tailor-made reactor design with the means of smart technology. Thereby, we aim the implementation of smart process control to yield autonomously operating bioprocesses, including surface-enhancing and stimuli-responsive materials from bulk chemicals, as shown in Figure 1, and additional integration of inline analytics in the form of UV and IR/Raman. Especially, stimuli responsive hydrogels in a 3D printed manner with encapsulated enzymes are investigated in cooperation with the Institute of Thermal Separation Processes (TVT, TUHH).

1) Hybrid reactor concepts – combination of reaction and downstream in one apparatus

Previously and in cooperation with the Institute of Multiphase Flows (IMS, TUHH) we could show that a geometrically forced guidance of reaction components in macro- and microscale can increase process efficiencies. A broad range of additive manufactured materials with distinct geometric properties lead to beneficial matrices for the utilization as enzyme carriers and flow distributors. The variety of materials and manufacturing techniques, tested in cooperation with the Institute of Laser and System Technologies (iLAS, TUHH), offers the possibility to select properties that are required for certain biocatalytic processes. In this approach the enzyme phenolic acid decarboxylase (PAD) from Mycobacterium colombiense was immobilized on different additively manufacturable matrices like polyethylene terephthalate by genetic supplement of anchor peptides. This technique was established together with the group of Ulrich Schwaneberg at the RWTH Aachen, Germany. Further, its immobilization on polyamide 12 has been successful, as well. By screening and prototyping of additively manufactured POCS the most suitable material was identified and used as extraction phase distributor in a counter current and multiphasic flow reactor, namely the PAD catalyzed synthesis of 2-methoxy-4-vinylphenol. By the presence of heptane as extraction phase a very efficient in situ product removal has been realized [2] (Figure 2).

2) Enhanced Surface Area Matrices

Targeting smart reactors, the 3D printed structures are used as backbone material for stimuli responsive polymer brush synthesis, these serve afterwards as a surface for enzyme fixation. Based on the implementation of a third dimension for binding an enzyme to the surface, the additively manufactured structures possess a greater surface-area-to-volume ratio, compared to untreated matrices. Therefore, increasing the amount of immobilized biocatalyst in a constant reactor volume. Additionally, the responsivity of those brushes enables autonomous process control by a change in conformation (coil-globule transition) based on e.g. decreasing or increasing pH values according to the reaction progress, resulting in a change of enzyme accessibility.

Both given examples have shown the potential of 3D-printing in biocatalysis with a wide range of possible applications. It could be demonstrated that recent issues and demands in e.g. continuous biocatalysis could be tackled when employing tailor-made 3D-printed material. Thereby, topics like flow regime regulating or autonomous in situ process control are certainly only the beginning.


  1. N. Büscher, G. V. Sayoga, K. Rübsam, F. Jakob, U. Schwaneberg, S. Kara, A. Liese, Org. Process Res. Dev. 2019, 23 (9), 1852 – 1859. DOI:
  2. N. Büscher, C. Spille, J. K. Kracht, G. V. Sayoga, A. W. H. Dawood, M. I. Maiwald, D. Herzog, M. Schlüter, A. Liese, Org. Process Res. Dev. 2020, 24 (9), 1621 – 1628
  3. D. Eixenberger, N. Büscher, X. Hu, A. Dawood, I. Smirnova, A. Liese, Chemie Ingenieur Technik 2020, 92 (9), 1223. DOI:

Associated with this project

  • Prof. Dr. A. Liese, head of the Institute of Technical Biocatalysis
  • Dr. A. Dawood, group leader of the group „Reaction Sequences“
  • D. Eixenberger and N. Büscher, PhD students