F R A U N H O F E R I N S T I T U T E F O R I N T E R F A C I A L E N G I N E E R I N G A N D B I O T E C H N O L O G Y I G B ANNUAL REPORT ANNUAL REPORT 2018 | 19

ANNUAL REPORT 2018 | 19

5 6 C H E M I S T R Y A N D P R O C E S S I N D U S T R Y 6 6 E N V I R O N M E N T A N D E N E R G Y 60 Application of laminarin from microalgae in plant 70 Case studies on water reuse in hydroponic green- production and human and animal nutrition houses 60 Superheated steam drying of food products at 70 Cooperation with India through the Water Innova- atmospheric pressure tion Hub 61 BIOTRAIN – A new perspective for sustainable 71 MOST – Model-based process control of biogas industrial value creation 61 Cellobiose lipids – Microbial biosurfactants from sugars plants: Practical tests 71 HoLaFlor – Increasing the efficiency of biogas plants 62 Driving on bark, building with nutshells 72 High-load digestion at the Leipheim sewage treat- ment plant 72 Innovative cascade processes for CO2 conversion 73 PICK – Plasma-induced CO2 conversion into fuels and chemicals 62 High concentrations of xylonic acid through process optimization 63 Separation and purification of furan derivates from coupling streams containing lignocellulose 63 Malic acid made of xylose – fermentation at 1 m3 64 CELBICON – Cost-effective carbon dioxide conversi- scale for the first time on into chemicals 64 Single-stage electrosynthesis of ethylene from CO2 65 Screenig of heterogeneous catalysts for energy conversion application 74 Further data and facts 76 Information service 77 Editorial notes 5

In several programs within Fraunhofer-Gesellschaft, we have assumed responsibility for impor- tant future topics, for example in the Life Sciences Group. At the national level, IGB is active in numerous committees, in particular within the framework of bioeconomic topics. Interna- tionally, we are involved in various project center initiations on the topics of “Drug Discovery and Delivery” in Israel, “Water and Environment” in South Africa and “Sustainable Chemical Products from Solar Energy” in Morocco. Parallel to our medium- and long-term initiatives for the future, we initiated and successfully implemented a whole series of positive changes at the institute last year. Some development projects were successfully completed, exciting new projects were launched. Selected examples can be found in this report. Additionally, we have also initiated many organizational changes and restructured internal processes in recent months. Mr. von Ritter zu Groenesteyn, who brings with him many years of experience in the administration of research organizations, has been appointed to manage the administration. Mr. von Ritter will start his work at IGB in April 2019. But most important for the sustainable development and success of IGB are its employees and their commitment to the institute. It is very important to me to further strengthening the con- cept of working with and for each other and to experience it in daily practice. We are on the right path. I would therefore be delighted if this annual report could inspire you to new cooperations and the continuation of established partnerships with IGB. Markus Wolperdinger Director 7

2 Fraunhofer Groups 19 Members of Advisory Board 5 Departments 8 Fraunhofer Alliances 2 Branches of the institute 45 % Proportion of women 388 Employees 6 BOGY high school students 62 University employees 37 Doctoral students 24 Apprentices 26 Nationalities 95 Students 326 Fraunhofer employees € 1.7 million Investments € 13.9 million Personnel costs € 26.5 million Total budget 61.2 % Own revenues € 10.9 million Non-personnel costs

BOARD OF TRUSTEES T h e F r a u n h o fe r I n s t i t u t e s a r e a d v i s e d b y b o a r d s o f t r u s t e e s w h o s e m e m b e r s a r e d r a w n f r o m i n d u s t r y, pu b li c au t h o r i t i e s , and t h e s ci e nt i f i c co mmuni t y. Members (as of December 31, 2018) Prof. Dr. Elke Guenther Federal Ministry for the Environment, MinDirig Dr. Jörg Wagner Dr. Susanne Arbogast Indivumed GmbH Prof. Dr. Sara Brucker AIT Austrian Institute of Technology Nature Conservation and Nuclear Safety GmbH (BMU) Dr.-Ing. Bernd Krause (until June 30, 2018) MinR Dr. Joachim Wekerle Ministry of Economic Affairs, University Hospital Tübingen Gambro Dialysatoren GmbH Labour and Housing of the State of Baden-Württemberg Dr. Gerd Eßwein Dr. Caroline Liepert MinR Dr. Hans-Jürgen Froese Arts of the State of Baden-Württemberg Wacker Chemie AG Ministry of Science, Research and the Dr. Günter Wich Federal Ministry of Food and Agriculture (BMEL) Dr. Christian Naydowski Prof. Dr. Karl-Heinz Wiesmüller EMC microcollections GmbH Prof. Dr. Matthias Frosch Prof. Dr.-Ing. Dr. h.c. Dr. h.c. (until February 1, 2018) Prof. E.h. Michael Resch Dr. Wieland Wolf Faculty of Medicine, University of Institute of High Performance ProBioGen AG Würzburg Computing, University of Stuttgart MinDirig Dipl.-Ing. Peter Fuhrmann Prof. Dr. Dr. h.c. Ralf Riedel Permanent guests (until May 1, 2018) Institute of Materials Science, Ministry of the Environment, Climate TU Darmstadt Protection and the Energy Sector of the Prof. Dr. Herwig Brunner (Former Director of Fraunhofer IGB) State of Baden-Württemberg Prof. Dr. techn. Günter Scheffknecht Dr. Jürgen Groß Robert Bosch GmbH Institute of Combustion and Power Plant Prof. Dr. Dieter Jahn Technology, University of Stuttgart (Chair of Advisory Board 1999 – 2013) Prof. Dr.-Ing. Ralf Takors Institute of Biochemical Engineering, University of Stuttgart 11 11

Infrastructure and laboratory equipment High-resolution 400 MHz NMR analysis Cutting-edge technologies and extensive, modern equip- ment are indispensable to our scientific work – and an added benefit for you as our customer. Our laboratories are designed for work up to biological safety level S2. A new building com- Molecular structure elucidation, reaction monitoring, low- temperature analysis Surface and particle analysis Characterization of chemical, physical and morphological missioned in 2017 has, among other things, roll-to-roll coating properties of surfaces, thin layers, powders, and particles plants and technical centers for aseptic work (foodstuffs), for the treatment of process waste water as well as for wastewa- Microbial evaluation ter and sludge treatment on a pilot scale. Testing of antimicrobial effects and photocatalytic properties of surfaces Spectrum of services Process, technology and product development From laboratory to technical and pilot scale Design, construction and demonstration of pilot plants Biochemical and biomolecular analysis Diagnostic microarrays, protein expression profiles, protein analysis using MALDI-TOF / TOF mass spectrometry (also quantitative) and prototypes Next-generation sequencing Implementation of new technologies Licensing of technologies and processes Studies and consultancy Feasibility studies and technology analyses Profitability studies and life cycle assessment De novo genome / transcriptome sequencing, meta-genomics and meta-transcriptomics, microbiomics, next generation diagnostics (infectious diseases, COPD, etc.) Cell biology analysis Cell characterization (also non-destructive), flow cytometry Analysis and testing services Testing of cytotoxicity / biocompatibility of R&D materials and industrial products, assessment of phototoxicity of substances Cell-material interactions Our broad range of biological and physical / chemical examina- and solutions tion methods makes the institute a versatile partner in the fields of medicine and pharmacy, food production and chem- istry as well as environmental and water analysis. Physico-chemical analysis Quality control, food analysis, trace analysis, analysis of resi- dues, environmental analysis, water analysis For detailed information on our analytical and testing services: www.igb.fraunhofer.de/analytics 1 3

Personal At the end of 2018, Fraunhofer IGB (in Stuttgart and its Development of staff members branches in Straubing, and Leuna) had a staff of 326 of which some 80 percent were scientific or technical employees. Women made up 48 percent of the total. 450 400 The Institute of Interfacial Process Engineering and Plasma Technology IGVP at the University of Stuttgart counted a staff of 62 as of December 31, 2018, predominantly scientists and doctoral students as well as technical staff and student re- search assistants. Women constituted 29 percent of the total. The employees of Fraunhofer IGB, of its branches, and of IGVP work together closely and have very culturally diverse backgrounds, with 31 staff members coming from 26 differ- ent countries outside Germany. Staff composition as of December 31, 2018 Scientists Technical staff Doctoral students Administrative and secretarial staff Apprentices Scholarship holders Work students / Master students / student apprentices Student research assistants 391 394 365 341 326 s 350 r e b m e m 300 f f a t s f o r e b m u n 250 200 150 100 50 0 84 92 75 76 62 2014 2015 2016 2017* 2018* Fraunhofer IGB IGVP * since 2017, without Translational Center, Würzburg branch Fraunhofer IGB IGVP 81 85 9 40 17 5 16 73 326 13 9 20 4 7 3 – 6 62 1 5

FRAUNHOFER CENTER FOR CHEMICAL- BIO, ELECTRO AND CHEMOCATALYSIS BIOTECHNOLOGICAL PROCESSES CBP, BIOCAT, Straubing branch Leuna branch Dipl.-Chem. (FH) Gerd Unkelbach Phone +49 3461 43-9101 gerd.unkelbach@cbp.fraunhofer.de Prof. Dr. Volker Sieber Phone +49 9421 187-300 volker.sieber@igb.fraunhofer.de Dr. Moritz Leschinsky Phone +49 3461 43-9102 moritz.leschinsky@cbp.fraunhofer.de Dr. Michael Hofer Phone +49 9421 187-354 michael.hofer@igb.fraunhofer.de Dr. Daniela Pufky-Heinrich Phone +49 3461 43-9103 daniela.pufky-heinrich@ cbp.fraunhofer.de Biocatalysis – Catalyst Design and Process Development Chemical Catalysis and Electrochemistry – Catalyst Design and Process Development Biotechnological Processes Chemical Processes Pretreatment and Fractionation of Renewable Feedstocks PHYSICAL PROCESS TECHNOLOGY ENVIRONMENTAL BIOTECHNOLOGY ATTRACT GROUP ORGAN-ON-A-CHIP AND BIOPROCESS ENGINEERING Dipl.-Ing. Siegfried Egner Phone +49 711 970-3643 siegfried.egner@igb.fraunhofer.de Dr. Ana Lucía Vásquez-Caicedo Phone +49 711 970-3669 analucia.vasquez@igb.fraunhofer.de Dr.-Ing. Ursula Schließmann Phone +49 711 970-4222 ursula.schliessmann@ igb.fraunhofer.de Jun.-Prof. Peter Loskill Phone +49 711 970-3531 peter.loskill@igb.fraunhofer.de Heat and Sorption Systems Physico-chemical Water Technologies Nutrient Management Aseptic Technologies Prototype Development Technical Microbiology Bioprocess Engineering in the Water Sector and Circular Economy Accredited Analytics 17

Fraunhofer Groups and Alliances Fraunhofer Cleaning Technology Alliance www.allianz-reinigungstechnik.de Fraunhofer Institutes working in related subject areas cooper- Fraunhofer Water Systems Alliance (SysWasser) ate as groups, foster a joint presence on the R&D market and help define the Fraunhofer-Gesellschaft’s business policy. Institutes or departments of institutes with complementary expertises collaborate in Fraunhofer “Alliances” to develop www.syswasser.de Fraunhofer Technical Textiles Alliance www.textil.fraunhofer.de business areas together and offer market solutions along the In addition, Fraunhofer Institutes carry out joint activities entire value chain. within Fraunhofer internal research programs. Examples of IGB’s involvement are the High Performance Centers “Mass Fraunhofer IGB is an active member of the Fraunhofer Group Personalization” (Stuttgart) and “Chemical and Biosystems for Life Sciences and, due to its strong focus on materials Technology” (Halle-Leipzig region) as well as the Fraunhofer science, an associated institute of the Fraunhofer Group for lighthouse project “Electricity as a Raw Material” and those Materials and Components – MATERIALS. Furthermore, it is successfully completed like “Theranostic Implants”, “Critical a member of various Fraunhofer Alliances and thus optimally Rare Earths” and “E3-Production”. integrated within the Fraunhofer network. Fraunhofer Groups Fraunhofer Group for Life Sciences www.lifesciences.fraunhofer.de Fraunhofer Group for Materials and Components – MATERIALS (associated institute) www.materials.fraunhofer.de Fraunhofer Alliances Fraunhofer Energy Alliance www.energie.fraunhofer.de For further information on IGB’s networking activities: Fraunhofer Food Chain Management Alliance www.fcm.fraunhofer.de www.igb.fraunhofer.de/network Fraunhofer Additive Manufacturing Alliance www.generativ.fraunhofer.de Fraunhofer Nanotechnology Alliance For further information www.nano.fraunhofer.de on CBP’s networking activities: Fraunhofer Polymer Surfaces Alliance POLO® www.polo.fraunhofer.de www.cbp.fraunhofer.de/network 1 9

1 2 Fraunhofer lighthouse project “Critical Rare Earths” – Substitution, efficiency, recycling As a component of many high-tech products, rare earths are among the strategically most important raw materials for German industry. For a more efficient use of these valuable elements, eight Fraunhofer Institutes have developed new solutions in the now completed joint project. These include optimized manufacturing processes, concepts for recycling for CO2 reduction to ethylene and the gas diffusion electrode required for this purpose were developed. On the other hand, the electrosynthesis process could be successfully validated with a fully automatic demonstrator on 130 cm2 electrode area in flow-through operation (see p. 64). Fraunhofer Max Planck Cooperation Program eBioCO2n – Power-driven CO2 conversion through synthetic enzyme cascades for the production of processes and technologies, and new materials that can specialty chemicals replace rare earths. Fraunhofer IGB focused on the processing and reuse of recycled material from used magnets produced Not only chemical-catalytic processes can be considered for by hydrogen embrittlement. Biochemical and chemical leach- ing processes were optimized for the release of rare earths from the recyclate matrices and filtration membranes with selective adsorber particles were developed for concentration. We were able to show that particles coated with phospho- the current-driven synthesis of chemicals. It is also conceivable to combine CO2-fixing electron-transmitting biocatalysts with further enzymatic conversion steps in the form of an enzyme cascade for the production of fine chemicals. The “eBioCO2n” project, which was approved at the end of 2018 and is being nate groups, which were incorporated into the membranes, carried out jointly by Fraunhofer and Max Planck researchers, can be selectively enriched with Dy and Nd and can also be meets this challenge. The aim of this ambitious project is to demonstrate the feasibility of such bioelectrocatalytic syntheses with a demonstrator on a 10 – 100 mL scale. To this end, suitable CO2-fixing enzymes are to be assembled on electrodes (cathodes) using new molecular architectures and – depending on the target product – combined with other specific enzymes to form continuous and coupled reac- tion cascades. Recently discovered redox enzymes, enoyl-CoA carboxylases / reductases (ECRs), are used as CO2-fixing bio- catalysts. They are among the most efficient CO2-converting biocatalysts described so far. selectively eluted again. A separation by type could then be achieved by means of the free-flow electrophoresis developed in-house. Fraunhofer lighthouse project “Electricity as a Raw Material” – Ethylene from CO2 The expansion of wind power and photovoltaics associated with the energy revolution will further increase the supply of electricity from fluctuating energy sources. In the project “Electricity as a Raw Material”, ten Fraunhofer Institutes have developed new electrochemical processes to use excess electricity for the production of chemicals. In a subproject, Fraunhofer IGB has developed a process with which ethene, one of the most important chemical starting materials, can be produced electrochemically from CO2 and water in just one process step. For this purpose, novel, efficient catalysts 2 1

3 Energy Efficiency). The CO2EXIDE approach unites physicists, chemists, engineers and communication experts from five re- search institutions, two industrial enterprises and three SMEs in this project. Through their key technologies, they will make a contribution towards the development of an unprecedented process based on CO2, renewable energies and water, thus demonstrating that the chemistry sector can be synergetically combined with the energy sector. composite wood manufacturers: P2 particleboard and medium-density fiberboard. Fraunhofer IGB is participating in this BBI project with four other research institutions and five industrial partners, under the coordination of the RTDS Group. Completed projects In 2018, our first two Horizon 2020 projects, ELSi and Steam- Bio, were successfully finalized. New projects in Section III ”Societal Challenges” UNRAVEL 3 Perspectives Since June 1, 2018, Fraunhofer CBP has been coordinating the We have now already reached the year before the end of project UNRAVEL (see p. 62) in the public-private partnership Horizon 2020 and are also planning some new project sub- BBI, an abbreviation for Bio-Based Industries. Over the course missions in 2019. of the four-year project, ten European partners will develop advanced pretreatment, separation and conversion technolo- Furthermore, we are looking forward to the ninth Framework gies for complex biomass containing lignocellulose. Programme for Research and Innovation ”Horizon Europe” with great excitement and are participating in numerous pre- parative measures that are currently taking place. The project brings together specialists from a variety of fields who cover the entire value chain with their expertise. This includes the composition of the raw material, chemical pro- duction and pretreatment of wood pulp, enzyme production, polymer chemistry, separation and reactor technology, the techno-economic and sustainability assessment and the trans- fer, exploitation and communication of knowledge. SUSBIND Since May 1, 2018, the consortium SUSBIND has been de- veloping, producing and testing biobased binding agents as an alternative to the current fossil-based binders that often Contact contain formaldehyde, which are used for composite wood boards used in the manufacture of furniture. The aim of the project is to replace chemicals based on fossil raw materials with those from renewable resources. Excess raw material from existing European biorefineries will be used for the production of binding agents and interim products. Dipl.-Kffr. Jenny Ullrich Phone +49 711 970-4070 jenny.ullrich@igb.fraunhofer.de For further information on the Fraunhofer IGB EU-funded projects: SUSBIND has set itself the target of producing and validating these biobased binders for two types of product at leading www.igb.fraunhofer.de/eu-projects 2 3

2 To this end, a joint research project was started in November The following aspects, in particular, were discussed during the 2018 on the topic ”Synthesis of green hydrogen and green ammonia”. Partners in this ambitious approach, which, in meeting: First approaches to up-scaling of bark processing in New the future, might even replace the Haber-Bosch process that Zealand and consideration of their profitability. has been in common use for 100 years, are the Fraunhofer Development of products and identification of markets to Institute for Microstructure of Materials and Systems IMWS in build up a complete value-added chain through to end- Halle (Saale) in Germany, the Green Energy Park and the Insti- use applications. tut de Recherche en Energie Solaire et Energies Nouvelles, the Production of a SWOT analysis on the topic for the joint Université Mohammed VI Politechnique and the OCP Group in exploitation of opportunities. Morocco. The aim is to establish technology that can be used In a next step, a concrete project is to be worked out that will to sustainably synthesize ammonia: using nitrogen from the be driven forward in a joint effort when the SCION scientists air and hydrogen that is obtained through electrolysis of water come to IGB on their planned return visit in spring 2019. using regenerative energy. The kick-off meeting took place in Morocco on November 1 and 2, 2018 with Dr. Lénárd-Istvan Csepei as representative of IGB. Japan and Hong Kong – bioeconomy in the Far East Increased cooperation between African countries and re- Representatives of IGB and the CBP branch traveled to Japan searchers at IGB is taking up the Federal Ministry of Education and Research (BMBF) Africa strategy and hereby, in particular, strengthens collaborative research for the implementation of the United Nations Sustainable Development Goals, as well as for the exploitation of synergistic potential at national, Euro- pean and international levels, one of the United Nations’ five formulated central fields of action. and Hong Kong in October 2018 on behalf of the Fraunhofer Group for Life Sciences to discuss acquisitions in the fields of bioeconomy and industrial biotechnology. The IGB delegation was supported in Japan by Fraunhofer Representative Office Japan, such that the Institute was given the opportunity of introducing itself to well-known companies and laying the foundations for future cooperation. Successful collaboration between CBP and a Japanese biotechnology company serves as a model for this. In Hong Kong, initiated by the Fraunhofer New Zealand – bark as a raw material Group for Life Sciences, IGB representatives held discussions The global relevance of IGB topics was also revealed at a workshop in New Zealand: in June, a joint workshop took place there at the SCION Research Institute in Rotorua on the topic Bark Biorefinery, with scientists from IGB and CBP. The objective of this workshop was to develop a concept for the sustainable use of bark waste, as well as to establish connec- tions between stakeholders as actors in a potential value- with representatives of the Hong Kong PolyU on the creation of a joint project center. Collaboration in the fields of biocom- patible materials, industrial biotechnology and environmental process engineering is to take place at this center. added chain relating to the products of bark. Contact Dipl.-Agr.-Biol. Sabine Krieg MBA Phone +49 711 970-4003 sabine.krieg@igb.fraunhofer.de 2 5

1 Dr.-Ing. Christopher Probst successful with Retina-on-a- Student Teresa Krumm receives the Boehringer Chip at Sciene2Start Competition Ingelheim Award for her Bachelor Thesis Researchers at IGB and at the University of Tübingen have In November 2018, the student Teresa Krumm received a jointly succeeded in simulating the complex human retina study award from the pharmaceutical company Boehringer in a microphysiological system. The retina model created in Ingelheim for her bachelor thesis on “CRISPR / Cas9-induced this way will help to research new treatment options for eye knockout of thymidine kinase 1”. Krumm successfully com- diseases. IGB scientist Dr.-Ing. Christopher Probst, who works pleted her bachelor’s degree in pharmaceutical biotechnology at the Institute in the research group “Organ-on-a-Chip”, was at the University of Biberach with this thesis. For her thesis in charge of this ambitious project. With their “Retina-on-a- she worked at IGB in the research group Molecular Cell Technology and was supervised by group leader Dr. Anke Burger-Kentischer. Chip” innovation, Probst and his team from across different departments of the institute finished third in the Science2Start competition in summer 2018. This is hosted by BioRegio STERN Management GmbH, which is dedicated to promoting biotechnology and life sciences in Baden-Württemberg. Dr. Markus Wolperdinger speaks at 1 the Global Climate Action Summit 2018 At the Global Climate Action Summit in San Francisco in September 2018, international decision-makers from politics, research and industry met to discuss solutions to the problem of climate change. In addition to numerous celebrities from all over the world, Dr. Markus Wolperdinger also took part in the summit meeting and spoke as a guest speaker on the contribution of applied research to climate protection. The IGB institute director visited the summit as a member of a delega- tion from the state of Baden-Württemberg, which under the aegis of Prime Minister Winfried Kretschmann travelled to California and the Canadian region of Ontario to explore pos- sible economic and scientific cooperation. 2 7

2 3 Biointelligence – A new perspective for sustainable Current exhibitions value creation? As part of the Fraunhofer BIOTRAIN project (see p. 61), IGB and other Fraunhofer Institutes jointly investigated the possi- bilities of sustainable value creation through the application of materials, structures and principles of living nature in technol- ogy. The aim of this project was to analyze what contribution Energy Storage March 12 − 14, 2019, Düsseldorf ICE Europe March 12 − 14, 2019, Munich the biological transformation of industrial value creation can make to Germany as a business location. The results of this Hanover Trade Fair April 1 − 5, 2019, Hanover study were presented at the Fraunhofer Forum in Berlin at the end of June 2018. 3rd Joint Symposium on Nanotechnology April 9 – 10, 2019, Stuttgart Medical technology day 3 Chemspec Europe On medical technology day 2018 at the Fraunhofer Forum in Berlin, the Fraunhofer-Group for Life Sciences brought together Fraunhofer scientists and experts from politics and industry to provide information on current developments and June 26 – 27, 2019, Basel, Switzerland Biosurfactants International Conference September 25 − 27, 2019, Stuttgart challenges in biomedical technology. Hon.-Prof. Dr. Christian 22nd Colloquium on Wastewater and Waste Oehr, Deputy Director of IGB, represented the institute on the Treatment medical technology day and gave a lecture on the research October 8, 2019, Stuttgart focus of IGB: biofunctional materials, next-generation diag- nostics and organ-on-a-chip systems. K 2019 October 16 – 23, 2019, Düsseldorf parts2clean October 22 – 24, 2019, Düsseldorf SEPAWA Congress October 23 – 25, 2019, Berlin Bio-Europe November 11 – 13, 2019, Hamburg 2 9

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2 BOGY – Career and study orientation at the High School Dual training at Fraunhofer IGB Choosing the right profession is one of the most important In addition to young academics, trainees also enter the world decisions in young people’s lives. For this reason, high school of work at IGB, as non-university education is also a top students in Baden-Württemberg complete one-week BOGY priority at Fraunhofer. At the end of 2018, a total of 18 young short internships (vocational and study orientation at the high women and men completed vocational training at IGB and school) between grade 9 and 11, which are intended to pro- IGVP, IGB’s partner institute at the University of Stuttgart, vide them with orientation at an early stage. The Fraunhofer Institute Center in Stuttgart supports this initiative. Pupils with an interest in science and technology will gain an insight into the world of applied research and learn about study, career entry and career opportunities. For this reason, the Institute seven of whom were newly hired at IGB in 2018. The range of training occupations on offer is broad. Office management clerks learn their profession in the administration and IT spe- cialists are trained in the IT department. In the scientific field, the institute trains biology and chemistry laboratory assistants. Center arranges several BOGY internships at the Stuttgart The administrative trainees go through several stations at the institutes every year. In 2018, IGB accepted a total of six pupils on two dates in April and October. www.stuttgart.fraunhofer.de/bogy institute within three years. In this way, they get to know the different fields of work of a research institute and acquire all the necessary qualifications that are important for a later career in research or industry. In addition, IGB supports its trainees when they are aiming for a degree after completing Career day “The future lies in Sciences” 2 their training. www.igb.fraunhofer.de/ausbildung The Career Day of the Fraunhofer Institute Center in Stuttgart is aimed at students and university graduates. The event will focus on the various career entry opportunities for young academics. At the Career Day, participants learn that they can already enter applied research at Fraunhofer during their studies, after graduation or later as experienced profession- als. Fraunhofer employees at various career levels – research student, doctoral students and executives – report on their personal experiences as part of the “Insider Insights” and give valuable tips for starting a career. Furthermore, the guests re- ceive an insight into the daily work of Fraunhofer researchers during guided tours of the institute. For further information on promotion of young scientists and training: www.igb.fraunhofer.de/career 3 3

COMPETENCES FRAUNHOFER-GESELLSCHAFT Research of practical utility lies at the heart of all activities pursued by the Fraunhofer-Gesellschaft. Founded in 1949, With its clearly defined mission of application-oriented re- search and its focus on key technologies of relevance to the the research organization undertakes applied research that drives economic development and serves the wider benefit of society. Its services are solicited by customers and con- tractual partners in industry, the service sector and public administration. future, the Fraunhofer-Gesellschaft plays a prominent role in the German and European innovation process. Applied research has a knock-on effect that extends beyond the direct benefits perceived by the customer: Through their research and development work, the Fraunhofer Institutes help to re- inforce the competitive strength of the economy in their local At present, the Fraunhofer-Gesellschaft maintains 72 institutes region, and throughout Germany and Europe. They do so by and research units. The majority of the more than 26,600 staff are qualified scientists and engineers, who work with an annual research budget of more than 2.5 billion euros. Of promoting innovation, strengthening the technological base, improving the acceptance of new technologies, and helping to train the urgently needed future generation of scientists this sum, more than 2.1 billion euros is generated through and engineers. contract research. Around 70 percent of the Fraunhofer- Gesellschaft’s contract research revenue is derived from con- tracts with industry and from publicly financed research proj- ects. Around 30 percent is contributed by the German federal As an employer, the Fraunhofer-Gesellschaft offers its staff the opportunity to develop the professional and personal skills that will allow them to take up positions of responsibility and state governments in the form of base funding, enabling within their institute, at universities, in industry and in society. the institutes to work ahead on solutions to problems that will not become acutely relevant to industry and society until five or ten years from now. Students who choose to work on projects at the Fraunhofer Institutes have excellent prospects of starting and developing a career in industry by virtue of the practical training and International collaborations with excellent research partners and innovative companies around the world ensure direct access to regions of the greatest importance to present and future scientific progress and economic development. The Fraunhofer-Gesellschaft is a recognized non-profit or- ganization that takes its name from Joseph von Fraunhofer (1787 – 1826), the illustrious Munich researcher, inventor and experience they have acquired. entrepreneur. Figures are for January 2019. www.fraunhofer.de Fraunhofer headquarters in Munich, Germany. 3 5

Physical Process Technology Environmental Biotechnology and Bioprocess Engineering The department is involved in developing technologies, processes and process components based on physical and physico-chemical principles. A hallmark of our R&D activities is improving economic efficiency and sustainability of produc- tion processes at the same time – by minimizing material The core areas of the department are the development of (bio)engineering processes along the value chains in the fields of water management, wastewater treatment, bioenergy, environmental technology, algal technology, product recovery consumption, recovery of high-value substances in a quality from organic raw / waste materials and interfacial biology. equal to primary raw materials, and saving and reuse of Based on these processes, we are following new approaches energy. Our customers are either manufacturers of process to the development of system concepts for energy, waste and components, contractors, and process system suppliers, or industrial companies from sectors such as metal processing, the food industry, biotechnology and the water sector with a specific problem to be solved. water management in industry and for municipalities. The as- pects of resource and energy efficiency as well as integrative biorefinery concepts as defined by the bioeconomy approach are of particular importance to us when designing industrial processes. Technology and expertise Thermo-chemical heat-storage (adsorptive and absorptive) Evaporation and drying with superheated steam combined Technology and expertise Process development in bioreactors from laboratory to with winning of volatile fractions pilot and technical scale Stabilization of liquid food and biogenic products Cell-desintegration and extraction with high-pressure Development and operation of demonstration plants for aerobic and anaerobic wastewater treatment, high-load technique digestion, bioenergy, algal technology Chemo-physical water treatment (mechanical, electrolytic, Analysis of substrates and fermentation products, protein photolytic) analysis Primary / secondary winning of materials Processes and techniques to recycle organic and inorganic Real-time mass spectrometry Isolation and downstream processing of bioproducts products for agricultural applications Electrolytic and photolytic synthesis Electrophoretic separation of substances Integration of the technologies into customized processes Design, construction and operation of demonstrators (membrane-based filtration processes, process chromato- graphy, liquid-liquid extraction, extraction with supercritical CO2) Development and operation of apparatuses for testing antimicrobially finished materials Evaluation of microbial contaminations Process simulation and automation (Mat-Lab, Siemens) Contact Dipl.-Ing. Siegfried Egner Phone +49 711 970-3643 Contact Dr.-Ing. Ursula Schließmann Phone +49 711 970-4222 siegfried.egner@igb.fraunhofer.de ursula.schliessmann@igb.fraunhofer.de 3 7

Fraunhofer Center for Chemical-Biotechnological Processes CBP Fraunhofer CBP in Leuna develops and scales up chemical and biotechnological processes for the utilization of renewable raw materials – from upstream processing of raw materials and several conversion processes to separation and down- stream processing of transformation products. By making infrastructure and plants (pilot scale and miniplants) available and by providing high-qualified personnel, Fraunhofer CBP closes the gap between the lab and industrial implementation and makes it possible for partners from research and industry to scale up processes right up to production-relevant dimen- sions and thus to accelerate process developments. Technology and expertise Processing of raw materials – integrated pilot plant for pulping and fractionation of lignocellulose Biotechnological processes – modular process units up to 10 m3 reactor volume for fermentations Cultivation of microalgae in automated greenhouse and outdoor pilot plants, with a total volume of photobioreactors of 11.7 m3 Chemical processes – various process units for chemical reactions under ATEX conditions (continuous up to 20 kg/h or batch up to 100 liters) Downstream processing for separation, purification and reconditioning of products Contact Fraunhofer CBP Am Haupttor | Gate 12, Building 1251 | 06237 Leuna | Germany www.cbp.fraunhofer.de Dipl.-Chem. (FH) Gerd Unkelbach Phone +49 3461 43-9101 gerd.unkelbach@cbp.fraunhofer.de 3 9

16 Projects with universities, municipalities or funded by foundations 61Industrial projects 2 Fraunhofer lighthouse projects 32 Fraunhofer internal projects 49 Projects funded by German federal ministries 14 Projects funded by German states 194 Projects 20 EU projects

SUSTAINABLE VALUE CREATION THROUGH “BIOLOGICAL TRANSFORMATION” IGB: Pioneer and key player in biological transformation For more than 40 years, IGB has focused its work on the The “biological transformation” has long since begun. Like the development of biotechnological processes and biobased “digital transformation”, which has become an indispensable products, which are used in the medical, pharmaceutical and part of people’s everyday lives due to the Internet and the use diagnostic, food processing, chemical and renewable energy of smart phones, it has also changed production processes sectors, among others, based on the added social value of with new biological active substances in medicine and with new and sustainable products while maintaining functionality the systems approach of bioeconomy, which we will consider and quality. At IGB, industrial value creation and environ- separately because of its great importance for the Institute’s mental aspects were linked at an early stage as a solution for research strategy. In particular, the interaction between digital technologies and artificial intelligence on the one hand and the interconnection of life, materials and production sciences sustainable economic activity. With its commitment to the innovation process of biological on the other will make far-reaching innovations possible in the transformation, the Institute is actively addressing the chal- future. As an example, self-learning systems are conceivable lenges of biologized medical care for people and bringing whose learning processes are controlled by simulating pro- together individual value chains – “from raw material to cesses of real cells in combination with digital algorithms and product”, “nature’s own chemical plant”, “Nexus water, are used in the manufacture of completely new products. nutrition and energy” – to create holistic value creation cycles According to the definition given by Fraunhofer-Gesellschaft, biological transformation makes use of the principles, materi- for the production systems of the future. The abundance to which the Institute draws on in this respect is illustrated by the examples selected below for the various biological “system als and structures of living nature. These are not necessarily levels”. synonymous with the use of biological systems (cells, tissues) – as the highest level of integration. Rather, the production systems of the future will also be able to imitate and adapt the principles of biology or its materials and structures. This means that the production process of the future has learned from nature and its principles and processes and applies them to biotechnologically produced pharmaceuticals and “biolo- gized medicine” or – in the case of other sectors – in the sense of natural material cycles. 4 3

SYSTEM LEVELS OF BIOLOGICAL TRANSFORMATION AT IGB In future, new materials from the matrix of tissues, bioinspired structures and biofunctional or biologized surfaces will ensure that medical devices, prostheses and implants are better toler- ated. Materials that replicate the biochemical and mechanical Bioinspired materials and biologized surfaces properties of natural tissues can minimize irritation in the organism and prolong the shelf life of medical devices: In Wherever materials come into contact with biological systems, the future, materials will be available that can be fully inte- the properties of the materials and their interaction with the grated by the body, making them both patient-friendly and physiological environment play a decisive role. In the case cost-effective. of medical devices, our focus is on the interaction at the interface between the technical and the biological system. Depending on the objective, we modify the surface of the Enzymes – Specific conversion under mild conditions material used in such a way that the function of the biologi- cal component is not only not impaired (biocompatible), but The catalysts of biological cells are enzymes, proteins that in many cases even supported (bioactive). Depending on bring about all chemical reactions in the metabolism. Enzymes whether the interfaces are to adhere to each other (implants) have conquered numerous areas of everyday human life, from or be moved against each other (joints), adequate mechanical detergents to shampoo and toothpaste. As sensors, they reli- properties are required in addition to the chemical properties to stabilize the bond. To optimize the mechanical properties, the third dimension comes into play. The two-dimensional boundary surface becomes a three-dimensional boundary phase. For this case nature has developed and combined special materials with ably measure pollutants and help determine the blood sugar content of diabetics. Biocatalysts are highly specific to the substrate being converted and can also be used to produce compounds that are chemically difficult to access. Due to this specificity, the biocatalytically prepared products are of high purity – no by-products are formed. unusual mechanical properties. One example is joints. With IGB uses enzyme reactions for its own developments, but its special viscoelastic properties, joint cartilage, together with synovial fluid or its defined viscosity, ensures that joints can fulfill their function even under greater mechanical and intermittent stress. The implementation of such systems in technology still requires a great deal of fundamental research. also produces new enzymes on behalf of customers. Develop- ment begins with the screening of suitable enzymes, e.g. in soil samples or in sequence databases. Once candidates have been found, bacteria or yeasts are used for the efficient pro- duction of the enzymes and the cultivation is optimized from Cartilage, for example, is anisotropic in its mechanical proper- laboratory to pilot scale. ties. We tackle this challenge with special printing techniques using “bioinks” developed at IGB. 4 5

Human tissue and organ models for game-changing Recovery and reuse – material cycles based on nature preclinical tests Tissues and organs consist of different differentiated cells which in each case take over specifi c functions for a common task via cellular communication and regulatory mechanisms. Waste does not arise in living nature. In the biological cycle, plants and microalgae from carbon dioxide and inorganic nutrients such as nitrogen, phosphorus and sulphur form organic matter by means of photosynthesis, which is used by In order to understand these mechanisms and be able to re- other organisms via the food chains to build up their biomass. produce them in a manageable system, we reproduce models of human tissues and organs in the laboratory, with which human physiology and its diseases can be reproduced much Through respiration and microbial degradation of dead or- ganic matter, CO2 and nutrients are fi nally available again for new biosynthesis cycles. better than in animal models. Complex models made up of human cells also contain compo- nents of the immune system and we use them as test systems IGB research at the “environment” system level is oriented towards natural material cycles that are not infl uenced or disturbed by humans. The aim of our concepts for the treat- for the development and evaluation of new pharmaceuticals. ment of wastewater, for example, is to recover ingredients in 3D tissue models can also be used to set up test systems a recyclable form. In our system approach “semi-decentralized with disturbed control and regulation mechanisms (e.g. from patient biopsies or via specifi cally modifi ed human cells), on which active substances that compensate for this disturbance can be validated. integrated water management” we use anaerobic microor- ganisms to convert the organic matter present in the waste- water into biogas. The remaining nutrients can be precipitated in a plant-available form or, with the purifi ed water, used for fertilizing irrigation. The cultivation of the smallest functional unit of an organ into artifi cial microfl uidic systems, so-called organ-on-a-chip sys- tems, is another new technology for providing meaningful test In addition to the wastewater treatment plants common in Western civilization today, in which nutrients are disposed of systems for drug development. IGB constructs such organ-on- in non-recyclable form instead of being processed for return chips from human induced pluripotent stem cells. These hiPS cells can be specifi cally differentiated so that tissue can also be obtained that cannot be isolated from primary biopsies. to the biological cycle, it is above all industrial agriculture that withdraws nutrients from the natural cycles. When the plants are harvested, the nutrients are removed from the Since the cells of the organ-on-chip in the micro-physiological agroecosystem and hardly any return takes place. This makes system react to drug candidates in the same way as would be the supply of synthetic fertilizers necessary. With our newly the case in the human organism, they are used to investigate patented technologies, we focus on the recovery of nutrients active substances that cannot be evaluated in animal experi- from wastewater and liquid manure, fermentation residues ments – and animal experiments can be increasingly replaced. and residual materials from the food industry and on agricul- ture that is oriented towards natural material cycles. 4 7

Faster and more precise diagnoses using molecular biological approaches or new opportuni- ties for recovery through individualized therapy approaches – one example is the coordinated interplay between a (“biologized”) implant and its physiological environment – are scientific trends that are becoming more important because of the increase in life expectancy. Hence, drug efficacy has to be improved, for example by optimizing formulations and targeted release of active ingredients at the sites where they are needed. Fraunhofer IGB is developing solutions in these research areas. The aim is to improve medi- cal care for patients and simultaneously reduce healthcare costs. One focus here is on the development of three-dimensional in vitro models from human tissues up to organ-on-a-chip systems, as human test systems allow conclusions about effects and side effects of potential drug candidates already in preclinical research and thus can replace animal experiments. Per- sonalized medicine is another promising field of application for organ-on-chips. Networking and cooperation With our expertise, we contribute to the Fraunhofer Group for Life Sciences’ offer of cover- ing R&D for drug development from initial screenings to the production of test samples. In addition, we are networked in the Fraunhofer Generative Manufacturing Alliance. With the Fraunhofer Project Center for Drug Discovery and Delivery @ Hebrew University of Jerusa- lem, Israel, we have an important partner for the identification of new immune modulators and their formulation for the fight against infectious diseases and immune-mediated diseases. 4 9

Drug development and test systems Diseases are often caused by faulty interactions among en- dogenous molecules – for example, due to modified receptors or enzymes playing a decisive role in cellular signal chains and metabolic pathways. Fraunhofer IGB has developed various screening systems – from simple cell-based assays to complex human tissue models with immune system components. These systems support the analysis of the interactions of dif- ferent cell types associated with autoimmune diseases such as psoriasis or dermatitis, for example, or host-pathogen interactions on the molecular level. As a result, we are able to identify new target structures for the development of antibiot- ics or for the modulation of a patient’s own immune system. To analyze the effects and side effects of potential active compounds, we are developing three-dimensional in vitro tissue models and organ-on-a-chip systems based on human primary or iPS cells. These systems help to replace animal tests and to increase the information value of preclinical results. In addition, we are developing processes to produce pharmaceutical proteins: from the establishment of new ex- pression vectors to strain development and purification of the pharmaceuticals. We are pursuing a new approach with the development of “therapeutic” viruses. In this field, we use the ability of viruses to kill cancer cells. At IGB, Virus Engineering is tailoring a modular oncolytic viral vector based on HSV1 for cancer therapy. 51

3 4 More reliable next-generation diagnostics for sepsis Organ-on-a-chip platforms for the examination of pathogens beige adipose tissue In sepsis management, fast treatment using the correct The activation of brown and beige adipose tissue (BAT) and antibiotic is crucial for patient survival. This, however, is not “browning”, (generation of BAT in white fat tissue depots) has always possible in a targeted manner, since using the current aroused great interest in biomedical research in the last few standard (blood culture) pathogen detection is successful in years. This is mainly due to the decoupling of the mitochondri- only approximately 30 percent of cases. Therefore, a novel, al respiratory chain in BAT, a biochemical process that is show- molecular diagnostic and bioinformatic method has been ing considerable potential for new therapeutic approaches, in developed at Fraunhofer IGB to detect DNA fragments of pathogens in patient blood using parallel sequencing (next- generation sequencing, NGS) and bioinformatic algorithms, allowing for highly-specific and sensitive identification of pathogens (fig. 3). particular to obesity and diabetes. However, studies with hu- man tissue are still rare and difficult to carry out at present. Concepts and technologies to examine browning for pharma- cological studies and personalized medicine currently exist only to a limited extent. As part of a recent clinical study in collaboration with the Uni- As part of a collaborative project supported by the German versity Hospital Heidelberg, we were successful in achieving significantly more positive results on pathogen identification with this technology compared to using blood culture (71 per- cent compared to 11 percent) in 50 patients with septic shock. A jury of independent intensive care specialists considered 96 percent of the positive NGS results to be plausible. According Academic Exchange Service (Deutscher Akademischer Aus- tauschdienst, DAAD), Julia Rogal, a Talenta-funded IGB junior scientist, has conducted research at the University of Califor- nia at Berkeley, USA, for two months and has developed an innovative microfluidic system (fig. 4) for the integration of (beige) adipose tissue. This BAT-on-a-chip makes a variety of to the jury, treatment of 53 percent of the patients would different assays possible, e.g. to examine activation / blocking have been adapted subsequently on the basis of these results, of the functionality of BAT, the induction of browning in since they were often over- or undertreated due to the empiri- white adipose tissue, and characterization of endocrine and cal antibiosis. In this group of patients not receiving adequate metabolic function of BAT. The BAT-on-the chip system opens treatment, the mortality rate was increased by 13 percent. up diverse possibilities as an in vitro model for general screens These concrete effects on patient treatment success convinc- ingly demonstrate the enormous potential of more reliable and sensitive pathogen diagnostics. The retrospective ob- servations will now be validated in a multicenter study with approximately 15 hospitals, expected to start in January 2019. to identify substances that induce browning, as well as for ap- proaches to examine patient-specific effects of therapy approaches. www.igb.fraunhofer.de/sepsis-study www.igb.fraunhofer.de/en/bat-on-a-chip Contact Dr. Silke Grumaz Phone +49 711 970-4084 silke.grumaz@igb.fraunhofer.de Contact Julia Rogal Phone +49 711 970-4085 julia.rogal@igb.fraunhofer.de 5 3

Combinatorial space of 180 properties Random sampling Filters of 5 properties Iterative elimination Optimized outcome Global minimum Best solution ensemble Exhaustive? Exhaustive search 60 molecules tested in cell-based assay potenzieller Antagonist 56 TLR9 antagonists 3 17 highly active TLR9 antagonists FPC_DD@HUJI: Drug discovery and formulation for infections and autoimmune diseases The “Fraunhofer Project Center for Drug Discovery and Deliv- ery” at the Hebrew University in Jerusalem, Israel (FPC_DD@ HUJI), which was approved in 2018, focuses on discovering of new and validation of identifi ed substances and nanoparticle delivery systems for virus infections and autoimmune diseases. A combination of computational chemistry (on the part of HU) and a patented reporter gene assay (from IGB) is used with the aim of fi nding new Pattern recognition receptor antago- nists (PRR) and / or agonists for modulation of the innate im- mune response. During the preceding project “JRHDD – Joint Research Hub for Drug Discovery and Delivery”, 17 potential antagonists with high IC50 value were identifi ed from the 1.8 million commercially available molecules, and these were registered for patent. Another focal point is the development of new therapeutic strategies against herpes simplex viruses (HSV). Herpes viruses cause lifelong latent infections in neuronal cells and cannot be eliminated at present. Substances such as antimicrobial peptides kill the virus but are also highly toxic to eukaryotic cells. For that reason, we develop liposomal formulations with optimal physico-chemical properties. These targeted liposomal transport systems (HU) are used for encapsulation of specifi c substances and siRNAs which block virus replication, and are investigated and analyzed using 2D and 3D cell-based test sys- tems (IGB). Initial navigator peptide phospholipid formulations have shown an improved delivery of the active substances to neuronal cells. www.igb.fraunhofer.de/en/fpc-dd Contact Dr. Anke Burger-Kentischer Phone +49 711 970-4023 anke.burger-kentischer@igb.fraunhofer.de 5 5

The chemical industry is one of the most important and research-intensive economic sectors in Germany. Many innovations in the automotive, electrical and electronic, construction and packaging industries would not be possible without the contributions of chemistry. More than all other sectors, the chemical and further processing industries are characterized by resource- and energy-intensive processes. The dependence on the import of raw materials, the limited availability of fossil resources worldwide – even in competition with energy use – and the need to consider the impacts on both climate and the environment mean that our research also emphasizes initiatives to make the use of fossil resources more efficient or to create substi- tutes for them. With new and optimized conversion processes, energy-efficient processing technologies, product-friendly stabilization processes and new products based on biogenic residues and microalgae, IGB addresses both the traditional chemical industries and also the food, feed and cosmetics industries. Networking and cooperation Our distinctive networking collaborations with other institutes of the Fraunhofer Groups for Life Sciences and for Materials and Components – MATERIALS, or the Fraunhofer Food Chain Management, Nanotechnology, Technical Textiles, Polymer Surfaces POLO® and Cleaning Technology Alliances, as well as with universities and other research institutions, guarantee competent approaches even to interdisciplinary tasks. 5 7

Electrochemical synthesis of chemicals Fraunhofer IGB has successfully developed fermentation and purification processes, for example, for C2 compounds (ethylene, acetic acid, ethanol) and C3 compounds (propylene, propanol, propanediol, propionic acid, lactic acid) as well as With the expansion of regenerative power generation, low- cost excess electricity is generated, which – as an alternative to storage – can also be used flexibly for the electrochemical synthesis of basic chemicals. For this purpose, we are develop- for dicarboxylic acids (malic acid, itaconic acid, furan dicar- ing catalysts and suitable electrodes, electrolysis processes boxylic acid), amino acids and proteins. Based on renewable and equipment. In the Fraunhofer lighthouse project “Electric- resources, algal lipids or biogenic residuals, we have suc- ity as a Raw Material”, for example, Fraunhofer IGB has devel- cessfully demonstrated new ways to produce basic materials oped an electrochemical procedure to produce ethylene in a (long-chain dicarboxylic acids, fatty acid epoxides, lactams) for single process step. An electrochemical cell in which hydrogen polymer production. Further examples are aromatics, lignins, peroxide can be produced from just water and air is already phenols and furans as well as extractives and their derivatives (terpenes, phytosterols, camphor), and gaseous and liquid hy- drocarbons such as methane, olefins and long-chain alkanes. We have acknowledged expertise in the microbial production of biosurfactants for use as detergents or emulsifiers. available as a prototype at the institute. In various other proj- ects, we use renewable electricity to bind atmospheric CO2 and convert it into chemicals. We are increasingly combining these electrochemical with biotechnical conversion processes. Functional surfaces and materials For the surfaces of many materials, e.g. industrial components or technical textiles, the desired properties are often different from those that are intrinsic for the bulk material. Fraunhofer IGB is decoupling volume and surface properties by interfacial process engineering. We give surfaces of polymers, ceramics or metals new properties by applying thin layers or creating defined functions on surfaces. For this purpose, we use gas phase processes (CVD, PVD, PECVD), wet-chemical processes or combined processes. For open-pored polymeric foams with functional groups, we have developed a single-stage synthesis strategy. 5 9

3 4 BIOTRAIN – A new perspective for sustainable industrial Cellobiose lipids – Microbial biosurfactants from sugars value creation Our current production systems, even when augmented by far-reaching digitalization, do not provide sufficient enablers to cater for the fair satisfaction of the material needs of finite resources of future generations. A transformation to sustain- Microbial biosurfactants such as cellobiose lipids (CL) can be produced by microorganisms on the basis of sugars. Due to their surface-active and antimicrobial properties, CLs may be used in cosmetics or cleaning agents. Based on these proper- ties, they have great potential as a sustainable alternative to able production methods with new materials, closed cycles petrochemically produced surfactants. In order to exploit this and the use of sustainable technologies seems more urgent than ever. potential, the Industrial Biotechnology Group at Fraunhofer IGB is developing fermentation and purification processes that allow the highest possible space-time yields and are therefore At the same time, the growing knowledge about biological economical. processes and the new possibilities of digitalization offer new potentials to integrate the biological, technical and informa- Using an Ustilago maydis strain, we were able to produce CL tional spheres. The “biological transformation of industrial value creation” is therefore understood as the systematic application of knowledge about biological processes for the purpose of holistic optimization of production systems. With the participation of six Fraunhofer Institutes, the BIO- TRAIN project identifies the strengths, weaknesses, oppor- tunities and risks of a biological transformation of industrial value creation for Germany as a business location. The com- concentrations of more than 20 g·L–1. These were transferred from the shaking flask to the reactor scale (1 L, 10 L) (fig. 4). A fraction with a high cellobiose lipid concentration was collected by continuously separating the foam produced during fermentation. If this foam fraction is purified directly, only seven percent of the solvent quantity is required for the extraction of the cellobiose lipids, compared to conventional purification of the entire reactor content. prehensive analysis is based on extensive literature research, The individual process steps are evaluated by means of a life over 120 interviews with national and international experts cycle analysis and a techno-economic assessment during the from research and industry as well as numerous workshops with a total of over 200 participants. On the basis of this analysis, base technologies and their potential are also exam- ined, and development paths as well as recommendations for course of development. With the aid of these assessments, process bottlenecks are identified and validated experimen- tally. The findings obtained serve to continuously improve the economy and ecology of the overall process. action and design are developed for the public sector. www.igb.fraunhofer.de/en/biotrain www.igb.fraunhofer.de/biosurfactants Contact Marc Beckett M. Sc. Phone +49 711 970-4074 Contact Dr.-Ing. Susanne Zibek Phone +49 711 970-4167 marc.beckett@igb.fraunhofer.de susanne.zibek@igb.fraunhofer.de 61

3 4 Separation and purification of furan derivatives from coupling streams containing lignocellulose Malic acid made of xylose – Fermentation at 1 m³ scale for the first time Biobased furan derivatives, such as 2,5-furandicarboxylic acid To date, malic acid has been used primarily in the food and (FDCA), are increasingly gaining in importance, in particular beverage industry. It improves the shelf-life of baked prod- as biogenic building blocks for polymer applications. The ucts and provides the sour taste of jams and juices. But it Fraunhofer Center for Chemical-Biotechnological Processes also boasts considerable potential as a building block in the CBP is conducting intensive research into the separation and purification of furan derivatives from process water of the hydrothermal conversion of raw materials containing chemical industry. Together with succinic and fumaric acid, it belongs to the group of C4 dicarboxylic acids. C4 acids can be converted into 1,4-butanediol (BDO) – an important precursor lignocellulose, using a variety of thermal, mechanical and for further conversion into a wide variety of chemicals, includ- physico-chemical separation methods. Intensive research and ing plastics, polymers and resins; the possible applications development has been carried out in projects including those for these chemicals range from golf balls to printing inks and funded by the German Federal Ministry of Education and cleaning agents. Research (BMBF), ”KomBiChemPro” and ”BBChem”, and the project ”SteamBio”, funded by the EU. Fermentative production of malic acid was developed through We use cross-flow membrane systems (fig. 3) to separate the dissolved and undissolved constituents. The aim is to separate polymers from monomers and to reduce the water content to optimize the purification process energetically. Cross-flow membrane filtration also plays a central role in the separation of temperature-sensitive substances, such as 5-hydroxymeth- the collaboration of the Industrial Biotechnology working group at Fraunhofer IGB and the Biotechnological Processes Group at Fraunhofer CBP. Fermentation was carried out with the fungus Aspergillus oryzae (fig. 4), which is designated as a harmless food additive according to the GRAS (generally recognized as safe) status of the US Food and Drug Adminis- tration (FDA). In addition to glucose, the strain can also utilize ylfurfural (5-HMF) and formic acid. Furfural derivatives can the C5 sugar xylose, which is the main component of hemicel- also be successfully separated from the process water using rectification, which we have demonstrated at the pilot scale with a throughput of 2.5 kg/h. Investigations into liquid-liquid extraction and adsorption/desorption revealed targeted sepa- ration of the carboxylic acids from furan derivatives. In this lulose and thus can be sourced from wood residues. Initially, the process was optimized at the laboratory scale; it was then established in stirred reactors and finally successfully scaled up to the 1 m³ scale using the substrate xylose for the first time. Downstream processing could be demonstrated using crystal- case, we were able to successfully demonstrate the essential lization. In doing so, several kilograms of malic acid were pro- feasibility of separating furan derivatives in process waters duced that are now available as a sample for application tests. from hydrothermal conversion up to the 100-liter scale. www.cbp.fraunhofer.de/en/furan-derivatives www.igb.fraunhofer.de/en/kombichempro Contact Christian Bartsch Phone +49 3461 43-9115 christian.bartsch@igb.fraunhofer.de Contact Dipl.-Chem. (FH) Gerd Unkelbach Phone +49 3461 43-9101 gerd.unkelbach@igb.fraunhofer.de 6 3

3 4 Screening of heterogeneous catalysts for energy conversion applications Due to the daily and seasonal differences between the avail- ability and consumption of regenerative energy, new energy storage scenarios are under intensive R&D. Methanol is a Two reactor systems are available for the screening of heterogeneous catalysts in gas phase reactions (fig. 3 + 4). A multi-purpose screening system with four parallel reactor versatile platform chemical and as an energy carrier it plays an tubes and online GC-MS analytics has been acquired. The gas increasingly important role in energy transition scenarios. For the synthesis of methanol from carbon dioxide and electrolyti- cally produced hydrogen, two processes for catalyst synthesis dosing enables the use of technically relevant syngas mixtures with various CO / CO2 / H2 / H2O ratios. The system makes pos- sible high throughput screening over catalysts and reaction were optimized at the BioCat branch of IGB. Various reactor conditions. It also allows evaluating the long-term stability systems are available for the subsequent screening of the of the catalysts under optimal operation conditions and to catalysts regarding their performance. quantitatively collect and analyze the liquid products. The The state-of-the-art coprecipitation of Cu-based catalyst precursors was tuned for continuous operation, enabling very significant energy, time and resource savings on the industrial scale synthesis (patent pending). Another innovative method design also makes it possible to carry out various other reac- tions including methanization, Fischer Tropsch synthesis, and chemical conversion of methanol to olefins or liquid fuels as well as ammonia synthesis. is based on dissolution of metal compounds in deep eutectic A single-tube system was designed and built for catalytic test- solvents, followed by carbonization (WO2016 / 180973A1). ing at atmospheric pressure. Two operating sizes are available, with maximum 1 g and 50 g catalyst loading respectively. The system enables the investigation of reaction cascades such as methanol synthesis coupled to the methanol-to-olefin process. www.igb.fraunhofer.de/screening-of-catalysts Contact Dr. Lénárd-Istvan Csepei Phone +49 9421 187-364 lenard-istvan.csepei@igb.fraunhofer.de 6 5

Against the backdrop of the global debate on water shortage and pollution, resource scarcity and climate change, resource and environmentally friendly economies are becoming more and more important. The transition to sustainable, environmentally friendly yet reliable supplies of clean water, food, raw materials, and energy is therefore one of the major challenges of society today – also in view of the global climate protection targets. In national and international projects with partners from research, industry and municipali- ties, Fraunhofer IGB is developing innovative processes, reactors and new technologies for a sustainable water supply and disposal system, especially for the treatment of industrial process water and municipal wastewater, for the reuse of residual and waste materials, and to improve energy efficiency by making use of waste heat and regenerative energy. The business area Environment and Energy thus stands for a variety of advanced technological developments that help to prevent emissions being released into the environment, to recycle raw materials and to develop regenerative energy, thereby combining cost effectiveness with sustainability. Potential solutions are, in some cases, linked with major topics in the business area Chemistry and Process Industry. Networking and cooperation At Fraunhofer IGB we are developing integrated material flow and energy concepts for industry, municipalities and entire regions with the aim of replacing historically evolved infrastructures by system solutions using the latest technologies. We are therefore actively involved in the Fraunhofer Alliances Energy, Water Systems (SysWasser), and the Morgen- stadt Initiative. Also, Fraunhofer IGB is outstandingly networked nationally through the Ger- man Water Partnership, and very well connected throughout Europe. In addition, we work together with the University of Stellenbosch, South Africa, in the field of water treatment and use, and also in India the relationships that have developed through various projects (see p. 70) are being intensified. 6 7

Conversion and storage of renewable energy To tap new regenerative energy sources, we develop innova- tive membrane technologies, for example for efficient ethanol fuel cells or economically viable osmotic power plants. For the The efficient generation of biogas from sewage sludge using anaerobic technologies is a key issue at IGB. We have already converted several sewage treatment plants of different sizes energy system turnaround to succeed, storing excess power to our high-load digestion process, thus enabling them to must be practicable. For this purpose, we develop catalytic generate their own electricity. We also use our know-how processes to convert electrical energy – especially by binding and reducing CO2 – to chemical energy reservoirs, for example longer-chained hydrocarbons. The flexible electrochemical synthesis of basic chemicals is also an option that we are about the fermentation of organic substances for the reutiliza- tion of residual matter from the food industry and agriculture. Small mass flows are becoming increasingly interesting as the energy sector is decentralized. exploring in various approaches (see Chemistry and Process Industry business area). In this context, biogas occupies a special position among re- tion and many industrial processes remains unused. To make newable energy sources. The mixture of methane and carbon excess waste heat available for temporally and spatially dioxide is not just used to generate electricity and heat in decoupled heat requirements, Fraunhofer IGB is working on combined heat and power (CHP) plants, but also – after sepa- thermo-chemical sorption systems for the long-term storage ration of high-purity methane – as a fuel or raw material for of heat. In many cases, waste heat that results from power genera- basic chemicals. Biogas can thus not only serve as a temporary energy store, but also link the energy sector with the mobility and chemicals sectors. For the separation of high-purity meth- ane from biogas, we are therefore investigating absorption and membrane processes that bind CO2 with high capacity, as well as new material recycling paths. 6 9

5 0 0 29 0 29 34 29 30 30 30 34 39 0 29 34 39 29 34 39 44 Zeit [d] Zeit [d] 44 Essigsäure 49 Zeit [d] Essigsäure Propionsäure Propionsäure Buttersäure Essigsäure Essigsäure Propionsäure Buttersäure CO2 25 25 25 20 20 20 ] l / l o m m 15 15 15 [ n o i t a r t n e z n o k e r u ä S 10 10 10 L L / / l l o o m m m m n n i i n n o o i i t t a a r r t t n n e e c c n n o o c c d d i i c c a a 3 3 34 39 44 39 44 49 1 Zeit [d] Zeit [d] 1 0 44 49 54 0 49 54 0 54 2 CO2 CH4 Propionsäure 54 8 8 8 Buttersäure 49 54 Essigsäure acetic acid acetic acid 0 Propionsäure propionic acid propionic acid Buttersäure CO2 butyric acid butyric acid CO2 CO2 CO2 CH4 CH4 CH4 CH4 7 7 7 6 6 6 5 5 5 ] h / N l [ g n u g u e z r e s a G 4 4 4 3 3 3 1,8 1,6 1,4 1,2 1 0,8 0,6 0,4 0,2 0 0 Buttersäure CO2 CH4 CH4 h h / / N N L L n n i i e e t t a a r r w w o o fl fl s s a a g g d * L / L N n i y t i v i t c u d o r p e n a h t e m 4 500 450 400 350 300 250 200 150 100 50 S V T g k / L N n i d l e i y e n a h t e m 5 5 5 0 0 0 29 29 29 34 34 34 39 39 39 44 44 44 Zeit [d] time in d time in d 49 49 49 54 54 54 Essigsäure Propionsäure Buttersäure CO2 CH4 2 2 2 1 1 1 0 0 0 methane yield productivity 10 20 30 40 50 60 70 0 80 dwell time in d MOST – Model-based process control of biogas plants: HoLaFlor – Increasing the effi ciency of biogas plants Practical tests The development goal of the subproject “Practical Tests” was to evaluate the possibility of increased operational safety in biogas plants through early detection of process disturbance, allowing a timely reaction and thus increasing the profi tability of biogas plants. Various operational conditions were experimentally simulated Biogas plants that use renewable raw materials as substrates are usually operated with hydraulic retention times of 40 days. Signifi cantly longer hydraulic retention times of up to 90 days are also not uncommon. The aim of the HoLaFlor research project was therefore to operate a biogas plant with shorter retention times at constant biogas rates and at the same time to increase methane productivity. on a laboratory and pilot plant scale. Relevant operational For a pilot-scale biogas plant with maize silage as monosub- changes were carried out and the effects on the process strate, short retention times of between 15 and 30 days and documented. The experiments focused on extreme situations corresponding organic loading rates of between 2.9 and in the biogas process, aimed at registering the individual reac- 5.8 g / L*d were achieved at Fraunhofer IGB. At the same time, tions through measurable parameters and, if possible, incor- porate the fi ndings into the simulation program developed by the project partner Helmut Schmidt University Hamburg. the conventional process with a retention time of 70 days was investigated in a reference plant. It was shown that the methane productivity could be increased from 0.9 NL / L*d to The results have clearly demonstrated the stepwise reaction that leads to biogas production (fi g. 3), which characterizes the direct correlation between the concentration of acids and the production of biogas. The data density of the online mea- surements allowed the identifi cation with minute-by-minute precision of the shift from one preferred metabolic pathway to another. In addition, further correlations were presented, 1.7 NL / L*d with increasing throughput for retention times of 15 to 30 days, without signifi cant losses in the methane yield. The corresponding methane yield was between 284 NL / kg TVS and 303 NL / kg TVS. In comparison, a productivity of only 0.4 NL / L*d was achieved in the reference plant with a reten- tion time of 70 days. The methane yield amounted 341 NL / kg TVS (fi g. 4). which are currently not shown in the standard models such as ADM1. The stoichiometric distribution of metabolic products is approximately correct, a thermodynamic consideration The results impressively prove that biogas plants using suit- able plant technology can be operated with signifi cantly shorter retention times and thus methane productivities can is also relevant in the more extreme cases of the anaerobic be achieved which are two to four times higher than with digestion process. conventional process and long retention times. www.igb.fraunhofer.de/en/most www.igb.fraunhofer.de/en/holafl or Contact Barbara Waelkens M. Sc. Phone +49 711 970-4124 Contact Dr. Brigitte Kempter-Regel Phone +49 711 970-4128 barbara.waelkens@igb.fraunhofer.de brigitte.kempter-regel@igb.fraunhofer.de 7 1

3 PiCK – Plasma-induced CO2 conversion The aim of this development is to make CO2 usable as a chemical raw material and for the chemical storage of energy, thus contributing to the climate targets aimed at. Using a cost-efficient and resource-saving combination of plasma and membrane processes, CO2 is split into O2 and CO, which can serve as a starting product for the synthesis of platform chemicals such as methanol. The membrane process is needed to prevent the recombination of CO and O2 to CO2. The focus of the work at IGB is on the development of a suitable membrane (fig. 3), which on the one hand efficiently separates oxygen and on the other can be used in the plasma. A mixed conductive ceramic material (LawCaxCoyFezO3–̀; LCCF), which has already been described in the literature as CO2-tolerant, was selected for the manufacturing of the membranes. Using an established wet-spinning process and subsequent sintering, for the first time gas-tight LCCF capil- laries were produced in a reproducible manner that are both CO2-stable (> 200 h) and suitable for the separation of oxygen (O2 permeance of 1.0 ml min–1 cm–2 at 900°C). The capillaries produced by Fraunhofer IGB were investigated at IGVP in a CO2 plasma. They show very good thermal stability and good oxygen permeability in the plasma (2.3 ml min–1 cm–2 at 1 kW). Such capillaries have not yet been described in the literature. The next step is to optimize the separation efficiency by increasing the membrane area in the plasma. This is done by increasing the number of hollow fiber membranes built into the plasma. www.igb.fraunhofer.de/en/pick Contact Dr. Thomas Schiestel Phone +49 711 970-4164 thomas.schiestel@igb.fraunhofer.de 7 3

85 Committee memberships 126 Strategic cooperations 86 Academic theses 49 Master theses 4 Dissertations 2 Student research studies 8 Internship reports 21 Trade fairs and events 23 Bachelor theses 2154 Followers on LinkedIn 1577 Followers on Twitter Detailed information www.igb.fraunhofer.de/data

EDITORIAL NOTES EDITORIAL TEAM TRANSLATIONS, PROOFREADING Dipl.-Wirt.-Ing. (FH) Antje Hetebrüg, Dr. Stuart Amor, Stuttgart, Germany Jan Müller M. A., Beckett Translations, CV36 5NZ, Long Compton, UK Dipl.-Des. Thaya Schroeder (picture), Textworks Translations, Manchester, UK Dr. Claudia Vorbeck Dr. Sabine Wacker | Wacker Translation, Aichwald, and the scientists referred to as authors or Germany contact persons. LAYOUT AND PRODUCTION Dipl.-Des. Thaya Schroeder PHOTO ACKNOWLEDGMENTS Bayerl, Günther: pages 12, 37, 59 Doering, Sven: page 59 Fogel, Walter: page 36 PRINTING Institut für sozial-ökologische Forschung (ISOE) Fraunhofer Verlag, Mediendienstleistungen, GmbH: page 70 Stuttgart, Germany EDITORIAL ADDRESS Kleinbach, Frank: page 7 Krötz, Rafael: pages 31, 48 Michalke, Norbert: page 62 Fraunhofer Institute for Interfacial Engineering Müller, Bernd: pages 36, 38 and Biotechnology IGB Dr. Claudia Vorbeck Nobelstraße 12, 70569 Stuttgart, Germany ö_konzept: page 44 Shutterstock: pages 18 / 19, 43, 47, 50, 52, 64 All other photographs and figures © Fraunhofer IGB / Fraunhofer-Gesellschaft BioEcoSIM®, ePhos®, foxySPEC®, NANOCYTES®, Morgenstadt® and POLO® are registered trademarks of the Fraunhofer-Gesellschaft zur Förderung der This annual report was printed climate neutral with angewandten Forschung e. V., München, Germany. inks based on vegetable oil. The paper used is 100% recycled and the raw materials come from sustainable Reproduction of any material requires the editors’ forestry. It is awarded the EU Ecolabel AT / 11 / 002 and consent. the Blue Angel. © Fraunhofer IGB, Stuttgart 2019 7 7