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 2019 | 20

ANNUAL REPORT 2019 | 20

53 Functional ingredients from algae for health-promoting 6 5 I N N O V A T I O N F I E L D S 54 food and as plant strengthening agent in viticulture Evaluation of a biorefinery approach for the production of fucoxanthin and EPA with microalgae 65 Fraunhofer-Gesellschaft 66 Cell and tissue technologies 54 Scale-up of microalgae-based processes and customized 66 In-vitro diagnostics production of functional ingredients 55 CELBICON – Coupling electrochemistry and biotechnology 55 56 to convert CO2 into value-added chemicals Synthesis of hydrogen peroxide in an electrochemical cell SynLink – Synthetic e-fuels as a key enabler for sector linking 56 Mixed matrix composite membranes for gas separation 5 8 E N V I R O N M E N T 60 Streets of the Future: Environmental Monitoring 60 Morgenstadt Global Smart Cities Process control of blue-green infrastructures in Leipzig 61 61 Water reuse in agriculture – HypoWave project successfully completed 62 Reactor for the elimination of micropollutants in wastewater by oxidation 62 NextGenBiogas – Flexible production of bioenergy can contribute stability for power grids 67 Virus-based technologies 67 Functional ingredients 68 Water technologies and resource recovery 68 Membranes 69 Functional surfaces and materials Regenerative resources Industrial biotechnology 69 70 70 Catalysts 71 Bioinspired chemistry 7 2 I N F O R M A T I O N 7 3 E D I T O R I A L N O T E S 5

To this end, we have designated so-called innovation fields that straddle our business areas and our sites. This means we can push ahead with innovative ideas and the projects they spawn not only faster but also more efficiently. What defines these new innovation fields is their depth of focus, the expertise of the people who work in them, and their business potential. We are now in our first year following restructuring. The reorganization of Fraunhofer IGB applied to our strategy, the scope of our research, and each of our sites. This process of change is not yet complete, but positive changes are very much in evidence. This year, for example, we have been able to acquire significantly more projects in industry than the year before, as well as set in mo- tion various new projects. Our economic performance has improved substantially, and we have laid the foundations for further improvements. Among a raft of successful projects, I would like to single out the following: the continuation of our long-established cooperation with industrial partners from abroad at our site in Leuna (Sustainable Chemistry), the opening in Israel of a Project Center for Drug Discovery and Delivery (Health), and the preparation for the launch in South Africa of an Innovation Platform for the Water-Energy-Food Nexus (Environment), which is scheduled to open officially in the first quarter of 2020. These and other exciting projects are presented in this year’s annual report. Yet most important of all for the successful and sustainable future of Fraunhofer IGB are our em- ployees. We must therefore continue to work with and for one another – and continue to build upon this ethos in the future. I would like to extend my sincere and heartfelt thanks to all the staff of the institute and to all those who have supported our work. It is your efforts that have made possible the many positive changes of the past year. I will be delighted if this annual report inspires you to deepen established partnerships or embark on new collaborative ventures with Fraunhofer IGB. Markus Wolperdinger Director 7

… by using energy-efficient physical processes for the cell disruption of microorganisms to extract functional ingredients. Cell disruption is carried out at room temperature by pressure change technology. In doing so, microorganism cells are destroyed, their ingredients however are not changed. Dr. Ana Lucia Vásquez-Caicedo … by analyzing substrates, metabolites and products of biotechnological conversion processes from the solid and liquid phase in real time and with low measurement noise. This enables us to completely map the course of biotechnological reactions. By means of analyses, process understanding is increased and data can be provided for both upscaling and (model-predictive) control of processes. Dr.-Ing. Matthias Stier, Johann Barlach, Stephan Scherle, Steffen Görner ... by using bacteriophages specifically for the degradation of biofilms and thus selectively reduce the bacterial contamination of technical systems. apl. Prof. Dr. Susanne Bailer

PROFILE WE COMBINE BIOLOGY AND ENGINEERING What can we do to put an end to the shameful waste of the What we stand for planet’s natural resources and to help combat climate change? How can we assure an equitable supply of food, water, and raw materials to the worlds growing population And what can we do to improve the accuracy of diagnostic methods used to detect infectious diseases and cancer, provide af- fordable and ethical drug testing, and develop personalized medicine for an ageing society? Our mission: Sustainable technologies for human health and the health of our planet Fraunhofer IGB seeks out answers to these questions by de- veloping and optimizing processes, technologies and products in three business areas: Health, Sustainable Chemistry, and Environment. In doing so, the institute relies on its unique combination of expertise in biology and the engineering sciences, unparalleled within the Fraunhofer-Gesellschaft. This allows us to design resource-efficient, closed-loop pro- cesses based on the systems approach of bioeconomy and bioinspired, biointegrated and biointelligent ideas, in order to contribute to human welfare, a sustainable economy, and an intact environment. Bioengineering as the basis of tomorrow’s healthcare system Under the heading Smart Health Engineering Fraunhofer IGB aims to develop new molecular- and cell-biological tools for the precise diagnosis of cancer and infectious diseases, and develop new approaches to personalized medicine. The IGB’s test systems based on human cells and tissue are innova- tive models that allow the efficacity of new therapeutic drugs to be assessed with a high degree of certainty, and with the aim of replacing animal testing in the long term. Climate-friendly / -adaptive processes and products The IGB applies the bioeconomic approach to its research into sustainable methods of producing wholesome food and animal fodder. The same approach is taken toward biofuels, fine chemicals and primary raw materials – all of which con- tribute to the establishment of a sustainable, climate-friendly system of production. Our carbon-neutral solutions make use of renewable resources such as aquatic microalgae, and even carbon dioxide, which can be a useful raw material in decentralized production units. Other ways of reducing CO2 emissions and mitigating climate change include exploiting biogenic waste streams. Their physical conversion is increas- ingly possible using renewable energies. The circular economy and resource efficiency Life on this planet is based on natural cycles. Fraunhofer IGB studies these cycles in order to develop efficient methods and innovative components of technological systems designed to preserve global resources – from the harvesting of raw materi- als and their processing into products to their end-of-life dis- posal or reuse. Recoverable resources include not only carbon, 11 11

BOARD OF TRUSTEES T he Fraunhofer I ns titutes are ad vis ed by boards of trus te es whos e member s are draw n from indus tr y, public authorities, and the scientific communit y. Members (as of December 1, 1) Dr. Christian Naydowski Dr. Susanne Arbogast (until June , 1) Indivumed GmbH Prof. Dr. Sara Brucker University Hospital Tübingen Dr. Gerd Eßwein (until December 1, 1) Prof. Dr.-Ing. Dr. h.c. Dr. h.c. Prof. e.h. Michael Resch Institute of High Performance Computing, University of Stuttgart Prof. Dr. Dr. h.c. Ralf Riedel (until December 1, 1) Institute of Materials Science, TU Darmstadt Dr. Günter Wich Wacker Chemie AG Prof. Dr. Karl-Heinz Wiesmüller (until December 1, 1) EMC microcollections GmbH Dr. Wieland Wolf ProBioGen AG Permanent guests MinR Dr. Hans-Jürgen Froese Federal Ministry of Food and Agriculture (BMEL) Prof. Dr. techn. Günter Scheffknecht Institute of Combustion and Power Plant Technology, University of Stuttgart Prof. Dr. Herwig Brunner (Former Director of Fraunhofer IGB) Dr. Jürgen Groß Robert Bosch GmbH Prof. Dr.-Ing. Ralf Takors Institute of Biochemical Engineering, University of Stuttgart Prof. Dr. Dieter Jahn (Chair of Board of Trustees 1 – 1) Prof. Dr. Elke Guenther AIT Austrian Institute of Technology GmbH Dr. Caroline Liepert Ministry of Science, Research and the Arts of the State of Baden-Württemberg MinDirig Dr. Jörg Wagner Federal Ministry for the Environment, Nature Conservation and Nuclear Safety (BMU) MinR Dr. Joachim Wekerle Ministry of Economic Affairs, Labour and Housing of the State of Baden-Württemberg Dr. Dr. h.c. Christian Patermann Director ret. EU Commission, MinDirig. ret. Dr. Joachim Schulze JS BioConsulting GmbH 1 3 1 3

Good laboratory practice (GLP) test facility Several non-clinical tests are running at our category GLP unit Cell-based test systems for the determination of biologi- cal parameters to support RD projects that investigate biological parameters of samples using cell-based assays. Analytics at a glance Our broad range of physico-chemical and biological examination methods turns the institute into a versatile partner for various analysis issues. Examples are: Testing of bioactivity, cytotoxicity and immunogenicity of compounds using immune receptor-based assays Physico-chemical analysis uality control, food analysis, trace analysis, analysis of residues, environmental analysis, water analysis Screening of TLR agonists/antagonists Testing of antimicrobial properties of substances or surfaces Detection of pyrogens and microbial residues (pathogen- Surface analysis Chemical, physical and morphological characterization associated microbial patterns, PAMPs) Detection of viruses Real-time process analysis Integrated in chemical and biotechnological processes Assessment of biodegradability Aerobic and anaerobic degradation tests Microbial evaluation Testing of antimicrobial properties of surfaces Biomolecular analysis Diagnostic microarrays, multiplex PCR systems for detection of pathogens Next-generation sequencing De novo genome transcriptome sequencing, meta- genomics and meta-transcriptomics, microbiomics, next generation diagnostics (infectious diseases, COPD, etc.) Cell-based test systems (see GLP test facility) Bioactivity, cytotoxicity, immunogenicity 1 5 For detailed information on our analytical and testing services: www.igb.fraunhofer.de/analytics

Personnel At the end of 1, Fraunhofer IGB (in Stuttgart and its branches in Straubing, and Leuna) had a staff of of which some percent were scientific or technical employees. Women made up percent of the total. The Institute of Interfacial Process Engineering and Plasma Technology IGVP at the University of Stuttgart counted a staff of as of December 1, 1, predominantly scientists and doctoral students as well as technical staff and student re- search assistants. Women constituted 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 staff members coming from 1 differ- ent countries outside Germany. Staff composition as of December 1, 1 Scientists Technical staff Doctoral students Administrative and secretarial staff Apprentices Scholarship holders Work students / Master students / student apprentices Student research assistants Development of staff numbers as of December 1, 1 450 400 391 394 341 326 339 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 2015 2016 2017* 2018 2019 Fraunhofer IGB, Stuttgart BioCat, Straubing Fraunhofer CBP, Leuna TZKME, Würzburg since 1, without Translational Center, Würzburg branch Fraunhofer IGB, (including branches) BioCat, Straubing branch Fraunhofer CBP, Leuna branch 32 1 339 1 1 2 1 0 11 48 1 32 1 6 1 0 6 66 17

HEADS OF INNOVATION FIELDS Functional Surfaces and Materials Catalysts Virus-based Technologies Dr. Michaela Müller Phone 11 -1 michaela.mueller@igb.fraunhofer.de Dr. Arne Roth Phone 1 1-1 arne.roth@igb.fraunhofer.de apl. Prof. Dr. Susanne Bailer Phone 11 -1 susanne.bailer@igb.fraunhofer.de Functional Ingredients Membranes Water Technologies and Resource Recovery Dr. Ulrike Schmid-Staiger Phone 11 -111 ulrike.schmid-staiger@ igb.fraunhofer.de Dr. Thomas Schiestel Phone 11 -1 thomas.schiestel@igb.fraunhofer.de Dr.-Ing. Marius Mohr Phone 11 -1 marius.mohr@igb.fraunhofer.de Industrial Biotechnology Bioinspired Chemistry Cell and Tissue Technologies Dr.-Ing. Katja Patzsch Phone 1 -1 katja.patzsch@cbp.fraunhofer.de Dr. Michael Richter Phone 1 1- michael.richter@igb.fraunhofer.de In-vitro Diagnostics Regenerative Resources Dr. Kai Sohn Phone 11 - kai.sohn@igb.fraunhofer.de Ulrike Junghans M. Sc. Phone 1 -1 ulrike.junghans@cbp.fraunhofer.de Dr. Anke Burger-Kentischer Phone 11 - anke.burger-kentischer@ igb.fraunhofer.de Jun.-Prof. Dr. Peter Loskill Phone 11 -1 peter.loskill@igb.fraunhofer.de 1 9

Fraunhofer Groups and Alliances Fraunhofer Polymer Surfaces Alliance POLO® www.polo.fraunhofer.de Fraunhofer Cleaning Technology Alliance www.allianz-reinigungstechnik.de Fraunhofer Water Systems Alliance (SysWasser) www.syswasser.de Fraunhofer Technical Textiles Alliance www.textil.fraunhofer.de In addition, Fraunhofer Institutes carry out joint activities within Fraunhofer internal research programs. Furthermore, the IGB is involved in the High Performance Centers Mass Personalization (Stuttgart) and Chemical and Biosystems Technology (Halle-Leipzig region). Fraunhofer Institutes working in related subject areas cooper- ate as groups, foster a joint presence on the RD market and help define the Fraunhofer-Gesellschafts business policy. Institutes or departments of institutes with complementary expertises collaborate in Fraunhofer Alliances to develop business areas together and offer market solutions along the entire value chain. Fraunhofer IGB is an active member of the Fraunhofer Group for Life Sciences and, due to its strong focus on materi- als science, it also counts as an associated institute of the Fraunhofer Group for Materials and Components – MATERI- ALS. Furthermore, it is a member of various Fraunhofer Alliances and thus optimally 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.igb.fraunhofer.de/network www.fcm.fraunhofer.de Fraunhofer Additive Manufacturing Alliance www.generativ.fraunhofer.de Fraunhofer Nanotechnology Alliance www.nano.fraunhofer.de For further information on CBP’s networking activities: www.cbp.fraunhofer.de/network 2 1

1 2 3 In addition, there is the basic scalability of algae production using artificial illumination. The fatty acid-rich algae biomass required for polymer synthesis in the project is to be produced and purified up to the FAME mixture (Fatty Acid Methyl Ester). NewFoodSystems Room for Innovation NewFoodSystems wants to ensure future nutrition and health with production processes that protect the climate and resources. Algae, insects, plants, and fish serve as suppliers of raw materials from which, after appropriate processing, marketable products for the feed and food industries are manufactured. In starting project , microalgae biopolymers such as starch, polyhydroxy butyric acid (PHB) and proteins will be developed for use in food, feed and food packaging and qualified for use in other applications. Processes for the phototrophic, mixotrophic and heterotrophic production of algal biomass are being developed for both in- novation rooms. For this purpose, residual material flows from food and feed production and lignocellulose processing (sugar mixtures) are to be evaluated as a source of carbon. IGB has already developed suitable processes for both fatty acid-rich and starch-rich algae. IGB researchers secure EXIST funding Spin-off company Variolytics 3 Under the name Variolytics, IGB engineers are planning a spin-off company to launch their real-time mass spectrometer developed at the IGB. The spin-off company will be funded for two years with 1. million euros from the EIST – Ex- istenzgründungen aus der Wissenschaft funding program of the German Federal Ministry for Economic Affairs and Energy (BMWi). The team of founders includes Dr. Matthias Stier, Steffen Görner and Stephan Scherle and Johann Barlach. With the newly developed mass spectrometry system Vario- lytics, up to thirty different substances or components can be analyzed in real-time. And this does not only apply to the gas phase but also to the liquid phase. This is a novelty on the spectrometer market, made possible by an innovative and pat- ented inlet system. The new mass spectrometer thus opens up a whole range of previously inaccessible fields of application, also for the Process Industry .. At Fraunhofer IGB it could be shown that the mass spectrom- eter can be successfully used in biotechnological applications to measure both reactant and product concentration simul- taneously. This makes it possible to directly measure, monitor and control reactions. Areas of application for real-time ana- lytics are the food, pharmaceutical, and chemical industries as well as water and environmental analysis. 2 3

1 Outlook The year is also the last year of Horizon and, as in previous years, offers a variety of opportunities to submit project proposals by or with Fraunhofer IGB. IGB establishes global future laboratories through sustainable cooperation with international partners Sustainable scientific excellence is primarily the result of con- tinuous exchange with the best in the world. It develops as Furthermore, the structure, themes, and financial framework for the ninth framework program for research and innovation, Horizon Europe, is becoming more and more concrete. Fraunhofer IGB is looking forward to the publication planned for autumn 2020 to participate with new project ideas next a lasting and robust basis for the development of innovative solutions to global challenges – such as resource protection, climate and water conservation, health, and food security – if this exchange pursues joint long-term goals. Fraunhofer IGB is therefore intensifying and deepening its initiatives and year. projects with international partners and is continuously adding new ones. GreenUp Sahara – with water-saving hydroponics The GreenUp Sahara project is one of the new initiatives that breaks not only new ground in scientific and technologi- cal terms but also sets new standards in terms of its financing model. GreenUp Sahara aims to develop a water-saving hydroponic concept for vegetable cultivation in the Algerian desert. For this purpose, Marc Beckett from Fraunhofer IGB, together with his colleagues from the Fraunhofer Institutes UMSICHT and ISE, launched Fraunhofers first crowdfunding campaign. They were supported by the fundraising team of Fraunhofer-Gesellschaft. The initial funding target of 1, euros at the start of the project was achieved through the support of people. As a result, it will be possible to iden- tify suitable materials for a scalable hydroponic system with the local engineer, Taleb Brahim, and the WFP (World Food Program) from December 1. This represents the first step in the implementation of a sustainable hydroponic system for vegetable cultivation in desert regions. Funds are currently still being sought for further work by the ambitious team. www.startnext.com/greenup-sahara 2 5 Contact Dipl.-Kffr. Jenny Ullrich Phone 11 - jenny.ullrich@igb.fraunhofer.de For further information on the Fraunhofer IGB EU-funded projects: www.igb.fraunhofer.de/eu-projects

2 On the Fraunhofer side, the IGB has taken over the leadership of the center for the next five years with Director Dr. Markus Wolperdinger and business area coordinator Dr. Ursula Schliemann. The official opening is planned for the first quarter of . Besides the IGB, the Fraunhofer Institutes IOSB, IST, and ISE are also involved. The Fraunhofer Energy Al- liance is associated as another partner. As a result, Fraunhofer and the University of Stellenbosch are establishing their cooperation on a sustainable basis beyond their collaboration in the WASTEC project. ree ark as the rened raw material of the future The cooperation of colleagues from Fraunhofer IGB and CBP with the SCION Research Institute in Rotorua, New ealand, continues to gain momentum after two joint working meetings in New ealand and Germany. A concept for the sustainable recycling of bark waste and a first approach for the development of a networking structure of producers and users along a potential value chain of bark products has been established and will be further developed in joint projects. To this end, the international team of Fraunhofer and SCION scientists is writing a joint proposal that will be submitted to the new research program in New Zealand. In addition to the enormous potential for the environment that results from the joint activities, a sustainable partnership with one of the worlds largest wood producers is being developed on this basis for the IGB. Water and energy infrastructure for smart cities in India 2 With the Smart Water Future India project funded by the German Federal Ministry for the Environment (BMU), in which intelligent and sustainable water management strategies were developed for the city of Coimbatore in southern India, Dr. Marius Mohr, together with Indian experts, laid the founda- tions for providing urgently needed long-term solutions for needs-based water management in the region even beyond the project. For example, Mohr currently heads one of the Smart City Labs in Kochi, which was created as part of the Fraunhofer Morgenstadt initiative. The aim of this activity is to develop transferable and, at the same time, financially viable roadmaps to reduce greenhouse gases, strengthen resilience to the consequences of climate change and improve the quality of life of the local population. The City Labs, with their science-based analysis methods, are the core of the Mor- genstadt tools. Continuity for joint activities is provided by a Memorandum of Understanding signed by the Indian Council of Scientific and Industrial Research CSIR and Fraunhofer- Gesellschaft during the Indo-German-Consultations. The event was attended by German Chancellor Dr. Angela Merkel, Federal Minister of Education and Research Anja Karliczek, and other high-level representatives of the ministries. Contact Dipl.-Agr.-Biol. Sabine Krieg MBA Phone 11 - sabine.krieg@igb.fraunhofer.de 2 7

CESIO congress award for Amira Oraby IGB receives Fraunhofer Family Logo In June 1 international experts for surfactants from research and industry met at the CESIO 11th World Surfactant Congress in Munich. This congress is hosted by CESIO, the European Committee for organic surfactants and their inter- mediate products. The latest edition of the event was also attended by researchers from the IGB, including Amira Oraby, who is a PhD student in the innovation field of industrial biotechnology and is researching the production of biosur- factants. Within the scope of the lecture program she gave a lecture on Integrated process design and optimization for the production of the biosurfactants cellobiose lipids from Ustilago sp. on renewable feedstocks. For this presentation she was awarded the CESIO 1 Oral Presentation Award in the category Technical Applications. In the summer of 1, the Fraunhofer-Gesellschaft created the Fraunhofer Family Logo as an internal qual- ity seal to recognize institutes that are an exemplary advocate of family-friendly working conditions. After all, a healthy work-life balance and thus a well-functioning work-life balance is of great importance to many em- ployees when choosing their workplace. The IGB also re- ceived this internal seal of quality in 1. A total of Fraunhofer institutes had applied for the award. The IGB is one of 1 institutes that actually received an award. In the opinion of the judges, the IGBs success in creating a framework for flexible working and a welcoming culture for women and men with children through a wide range of day care services was a strong point in favor of the Institute. Felix Derwenskus receives bioeconomy poster prize Since 1, numerous universities and research institutions in Baden-Württemberg – including Fraunhofer IGB – have cooperated in the Baden-Württemberg Bioeconomy Research Cluster. Its aim is to promote the transition to a sustainable RAUNHOFER FAMILIENLOGO way of doing business in the sense of the biobased economy at state level. The th status seminar of the research cluster took place at the University of Hohenheim at the beginning of 1. Several researchers from the IGB also attended the conference and contributed to the accompanying poster exhibition. Proven to be particularly popular, the poster by IGB scientist Felix Derwenskus on Microalgae biorefinery – cascaded fractionation of microalgae ingredients for food and feed applications was awarded a poster prize at the event. Institut D i e f o l g e n d e n 1 6 I n s t i t u t e w u r d e n u n t e r 4 0 E i n r e i c h u n g e n a u s g e z e i c h n e t u n d s t e c h e n j e w e i l s m i t m i n d e s t e n s 8 0 v o n 1 0 0 m ö g l i c h e n P u n k t e n h e r v o r : Fraunhofer-Institut für Eingebette Systeme und Kommunikationstechnik ESK Fraunhofer-Institut für Angewandte Festkörperphysik IAF Fraunhofer-Institut für Arbeitswirtschaft und Organisation IAO Fraunhofer-Institut für Chemische Technologie ICT Fraunhofer-Institut für Energiewirtschaft und Energiesystemtechnik IEE Fraunhofer-Institut für Experimentelles Software Engineering IESE Fraunhofer-Institut für Fertigungstechnik und Angewandte IFAM Fraunhofer-Materialforschung Institut für Grenzflchen- und Bioverfahrenstechnik IGB Fraunhofer-Institut für Integrierte Schaltungen IIS Fraunhofer-Institut für Integrierte Systeme und Bauelementetechnologie IISB Fraunhofer-Institut für Molekularbiologie und Angewandte Oekologie IME Fraunhofer-Institut für Optronik, Systemtechnik und Bildauswertung IOSB-AST Fraunhofer-Institut für Verkehrs- und Infrastruktursysteme IVI Fraunhofer-Institut für Verfahrenstechnik und Verpackung IVV Fraunhofer-Institut für elltherapie und Immunologie II Fraunhofer-Institut für Bildgestützte Medizin MEVIS Ort München Freiburg Stuttgart Pfinztal Kassel Kaiserslautern Bremen Leuna Erlangen Erlangen Schmallenberg Ilmenau und Görlitz Dresden Freising Leipzig Bremen 2 9

2 ManuFUTURE Workshop Current exhibitions* Under the motto The future of sustainable value creation systems, the European Technology Platform ManuFUTURE and the Fraunhofer-Gesellschaft organized a workshop on the Biological Transformation of the European manufacturing industry in Brussels at the end of June. The event brought to- gether around experts from industry, politics, and research to discuss how materials, structures, and processes of living nature can make manufacturing sustainable in the future. In this context, IGB Director Dr. Markus Wolperdinger spoke about the importance of using biowaste and renewable raw materials to achieve a climate-neutral circular economy. To- gether with Prof. Thomas Bauernhansl, Director of Fraunhofer Institute for Manufacturing Engineering and Automation IPA, Wolperdinger presented the modi of the Biological Transformation being pursued: bioinspired, biointegrated and biointelligent. Day of Bioeconomy 1 + 2 As part of the Innovations in the Life Sciences series of events, the Fraunhofer Group for Life Sciences brings together experts from science, industry, and politics with a focus on bioeconomy. Against this background, the Day of Bioeconomy was held in Berlin in September 1. In addition to the presentation of selected developments from the range of topics of bioeconomy, current challenges for re- search policy were discussed. High-ranking participants from industry, politics and associations also had the opportunity to talk directly to the drivers and actors of bioeconomy. The IGB, one of the central actors of the event, gave presentations on the topics Bioeconomy as a strategy for German industry, Water – the basis of bioeconomy and BioACCEPT – Bio- logical approaches for recycling management, production, and technology. BIOKET** March 1 – 1, , Lille (France) Energy Storage** March 1 – 1, , Düsseldorf Analytica March 1 – April , , Munich IFAT** May – , , Munich 9th Bioeconomy Conference** June 1 – 1, , Halle (Saale) Bioabfallforum (Biowaste Forum)** June – July 1, , Stuttgart 3rd International Bioeconomy Congress Baden-Württemberg** September 1 – , , Stuttgart-Hohenheim BIO World Congress September – , , Raleigh, North Carolina (USA) Colloquium on Wastewater and Waste Treatment** September , , Stuttgart SEPAWA** October – , , Berlin parts2clean October – , , Stuttgart * Subject to alternations ** With reference to the Science Year 2020 Bioeconomy 3 1

SCIENCE YEAR 2020 Bioeconomy is topic of the Science Year 2020 As a sustainable form of economic activity, bioeconomy is the economy of the future, and a transformation is inevitable. Our current economy based on fossil raw materials is reaching its limits. Global population growth and rising living standards are presenting us with new challenges – from anthropogenic climate change and the littering of the oceans to dwindling natural resources. We therefore urgently need to learn how to live and manufacture more sustainably. Bioeconomy provides the necessary solutions. Fraunhofer IGB is partner in the Science Year 2020 For more than years, Fraunhofer IGB has been research- ing the development and utilization of biological resources, processes and systems in order to provide methods for a sustainable, biobased economic system oriented on natural material cycles. Visit us at the MS Science Washing powder, washing-up liquid, skin creams, shampoos – they all contain surfactants. A large part of them is still produced from crude oil. The industry is therefore increas- ingly relying on surfactants from renewable raw materials, although these are mostly chemically produced. Fraunhofer IGB is investigating methods to produce biosurfactants on a biotechnological basis – using fungi. In this way, cellobiose lipids and mannosylerythritol lipids can be obtained, which are more versatile and better degradable than synthetic surfac- tants. The IGB is working to optimize the production process in order to increase the yield and reduce production costs. On board the MS Wissenschaft, we will be demonstrating our bio-washing machine in summer , which makes biology in detergents visible and tangible: fungi that produce bio- surfactants and the natural raw materials such as wood and Learn more about our concepts and strategies to combat oilseeds that provide the basis for the biosurfactants. climate change. Find out about current projects in which we are developing processes for manufacturing sustainable and biodegradable products. Find out about our activities to use alternative resources such as microalgae, renewable raw materials and biogenic residues, to recycle valuable materials or recover them for reuse. You are also cordially invited to our events and lectures. MS Wissenschaft is the floating Science Center of the German Federal Ministry of Education and Research. Every year, the exhibition ship tours Germany for four months to introduce the fascinating world of science to a broad public. In June , the MS Wissenschaft sets sail again – under the flag of the current Science Year Bioeconomy. www.igb.fraunhofer.de/bioeconomy 3 3 3 3

2 Fraunhofer HiWi-Days An integrated degree program at Fraunhofer IGB The Fraunhofer-Gesellschaft offers students the opportunity to take the first career steps while still at university. As re- search assistants, abbreviated HiWis (student assistants), they can gain professional experience at an early stage and work on application-oriented research projects – and thus lay the foundations for a career later on. With the HiWi-Days, which take place once a year, Fraunhofer also allows their student assistants an opportunity to look beyond the horizon of their institute and to get to know other Fraunhofer units and new topics. To show the full spectrum of Fraunhofer research, the event will take place at different locations. In May 1, Stuttgart was next. The program offered the participants nu- merous career and specialist workshops for further education and guided tours of the institutes. BOGY – Career and study orientation at secondary school Choosing the right profession is one of the most important decisions in the lives of young people. For this reason, second- ary school students in Baden-Württemberg complete one- week BOG short internships (vocational and study orienta- tion at the secondary school) between the th and 11th grade, which are intended to provide them with an orientation at an early stage. Fraunhofer Institute Center Stuttgart supports this initiative. Students with an interest in science and technology should be able to gain an insight into the world of applied research and find out about study, job entry, and career opportunities. For this reason, the Institute Center arranges several BOGY internships at the Stuttgart institutes every year. In 1, the IGB accepted one female and one male student. Fraunhofer not only offers young academics an entry into professional life – non-university training is also a priority. The same applies to the IGB: At the end of 1, the institute and the IGVP, its partner institute at the University of Stuttgart, employed a total of nine trainees. Also, seven young men and women have completed their apprenticeships in the course of this year. Fraunhofer also attaches great importance to equal- ity and the promotion of women, especially in the MINT sec- tor. It is therefore particularly gratifying that about two-thirds of the apprentices are female. The choice of occupations that require an apprenticeship is broadly diversified. Office man- agement clerks learn their profession in the Administration Department and IT specialists are trained in the IT Depart- ment. In the scientific field, the institute trains biology and chemistry laboratory assistants. In administration, the trainees pass through several stations within three years in order to get to know the different administrative work areas of a research institute. All trainees acquire the necessary qualifications for a later career in research or industry. Besides, the IGB also sup- ports its trainees if they wish to study after completing their training. For further information on promotion of young scientists and training: www.igb.fraunhofer.de/career 3 5

… through bioengineering and scaling up of biotechnological processes for the production of biobased basic, fine and platform chemicals (for further processing in the chemical industry or in the field of cosmetics, cleaning agents and plastics or adhesives). Dr.-Ing. Katja Patzsch … by developing a novel forming process for the produc- tion of miniaturized, tailor-made membranes as porous structures for the fixation and supply of human cells in microphysiological in-vitro tissue models. While the porous membrane structure is permeable for the transport of signal molecules for cell-cell interactions, it offers structure for the formation of a locally fixed, functional tissue. With such a carrier and supply structure, we aim to reproduce tissue as physiologically and miniaturized as possible and create novel test systems, e.g. for the development of pharmaceutical agents. Dr. Thomas Schiestel, Jun.-Prof. Dr. Peter Loskill ... by using DNA probes as biosensors on a test strip. In this way, the pathogens in question can be quickly and specifically diagnosed molecularly on site – even without a laboratory. apl. Prof. Dr. Susanne Bailer

The aim of the research work at Fraunhofer IGB is to introduce data-based algorithms – generated by machine learning meth- ods – to control the cultivation of algae in order to develop an economical, ecological and robust algae production process on an industrial scale. To achieve this goal, we are developing data-driven models not only for efficient production of algal biomass but also for their intracellular products. A reliable model will be developed that can well describe and predict algae growth for the automated and robust control of algae production processes. Data-based control is not yet widely applied to algae cultivation as in other areas such as fluid dynamics and bioinformatics . Most of the modeling of algae growth has been successfully completed at Fraunhofer IGB. Concept and results The modeling and control of the cultivation of microalgae is known to be more complex than that of bacteria or yeasts 1. This is mainly due to its complex growth behavior and the lack of robust online monitoring methods for the growth of microalgae. Improving monitoring of algae growth The most popular method for monitoring the growth of microalgae is the OD (optical density) sensor, which measures the light adsorption, scattering caused by algae cells to calculate the biomass concentration. However, algae cells can change their size, shape and pigment content under different growth conditions, which has a major effect on the accuracy of measurements with the OD sensor. The other challenge in the cultivation of microalgae is the big difference of the growth behavior in the laboratory and outdoors, as the conditions for large-scale outdoor cultivation are much more complicated than in the laboratory. Therefore, our focus is on improving online monitoring and modeling of large-scale microalgae cultivation with data-driven methods. To improve online monitoring, we are already optimizing the calibration of existing OD sensors with cultivation data under different conditions. However, OD sensors are very expensive and require an enormous investment for large-scale algae cultivation. For this reason, we are also developing other methods, for example using camera, RGB and soft sensors to estimate the biomass concentration. The goal is to develop a robust, cost-effective online monitoring system for the growth of microalgae with a minimum number of sensors in the cultivation system. 3 9

Original Growth Simulated Harvest Strategy original growth simulated harvest strategy 4 4 3,8 3.8 3,6 3.6 3,4 3.4 3,2 3.2 3 3 2,8 2.8 2,6 2.6 2,4 2.4 L / g n i n o i t a r t n e c n o c s s a m o b i 2 4 6 duration in d 8 10 12 2,2 2.2 0 2 Outlook The work carried out so far shows the possibility of predicting algae growth under complex outdoor conditions with a SVM- based model. The final goal is to develop a predictive model for microalgae production. It is clear that our model has the potential to control and optimize algae production on a large scale. However, the biggest challenge is the lack of reliable and inexpensive online sensors to monitor the content of the ingredients in algae cells. Therefore, our next step is to ana- lyze the content of the ingredients offline in the laboratory, and find the correlation to other available online measure- ments using mathematical methods. For example, a video camera or other optical sensors could be used for online de- tection of the color spectrum. A soft sensor can be developed with the online image data to estimate the concentration of the pigment in the cell using a machine learning model. Last but not least, the framework for using data-driven methods to optimize microalgae cultivation can also be applied to other bioprocesses, which means that our work is not only useful for microalgae, but also for other applications in biotechnol- ogy. Contact Yen-Cheng Yeh Phone 11 -1 yen-cheng.yeh@igb.fraunhofer.de Dr.-Ing. Matthias Stier Phone 11 - matthias.stier@igb.fraunhofer.de Literature 1 Bernard, Olivier, Francis Mairet, and Benot Chachuat. Model- ling of microalgae culture systems with applications to control and optimization. Microalgae Biotechnology (1): – . T. Duriez, S.L. Brunton, and B.R. Noack. Machine Learning Control–Taming Nonlinear Dynamics and Turbulence. Fluid me- chanics and its applications (1). P. Baldi and S. Brunak. Bioinformatics: the machine learning approach. MIT Press, 1. 1 Simulation of light distribution in a FPA reactor. 2 Example of an optimized harvest strategy in outdoor cultivation. The blue line represents the original growth of microalgae without any harvest strategy, in which 1.2 g/L biomass is formed in 12 days. The orange line shows the amount and the timing to harvest microalgae, which produces 1.77 g/L more than the one without a harvest strategy after 12 days. 41

SMART HEALTH ENGINEERING AND ENABLING TECHNOLOGIES FOR PRECISION MEDICINE Target markets Medical engineering Rounding off activities at Fraunhofer IGB is our work in the field of medical devices, which covers surface analytics and the development of functional surfaces and materials. Here, we focus on coating technologies, advanced materials and bio-inks for medical applications. In addition, we develop plasma and UV sterilization processes that enable highly ef- fective disinfection and removal of pyrogenic residues while conserving the material of the sterilization vessels. In our GLP test facility, we conduct nonclinical, category- tests (cell-based test systems for the determination of biolog- ical parameters) for all the fields named above. These include bioactivity, cytotoxicity and immunogenicity tests. We also operate clean rooms (ISO 5) for work in compliance with GMP guidelines. Fraunhofer IGB seeks to partner companies in the fields of diagnostics, medical engineering and drug development. Diagnostics Fraunhofer IGB has extensive experience in high-throughput sequencing for the diagnosis of sepsis, endocarditis and intraamniotic infection, and also for microbiome studies. Multicenter research trials are currently being conducted to validate our diagnostic procedure for sepsis. Drug development In the field of drug development, we develop human test systems that enable an evaluation of the effects and side effects of highly specific drug candidates at the preclinical stage of research, which would otherwise be impossible on the basis of animal testing. These test systems are based on in-vitro systems, ranging from three-dimensional in-vitro mod- els based on human tissue to organ-on-a-chip systems. Our wealth of experience in molecular cell technology has enabled us to develop highly precise receptor-based assays for drug validation and production cell lines for biologics. At Fraunhofer IGB, our many years of experience in virus engineering enable us to develop novel and innovative therapies based on customized viruses for targeted prevention (vaccines) and therapies (oncolytic viruses). For targeted drug delivery and release, we formulate active ingredients in, for example, a matrix consisting of biobased polymeric or silicate materials. Contact apl. Prof. Dr. Steffen Rupp Phone 11 - steffen.rupp@igb.fraunhofer.de 4 3

3 4 Development of test systems to screen for psoriasis therapeutics using bicyclic genetically encoded libraries Centrifugal heart-on-chip (HoC): A versatile platform for cardiac tissue generation and analsis The incurable, inflammatory skin disease psoriasis affects percent of the worlds population. Therapies have significant side effects such as systemic weakening of the immune system or limited patient response. Toll-like receptors (TLR) of the innate immune system play a key role in inflammatory skin diseases. For example, keratinocytes show increased TLR expression in psoriasis. In the Psobibi project, TLR antagonists for topical application are identified, synthesized and validated as an alternative to systemic psoriasis treatment. Despite considerable research efforts, cardiovascular diseases still constitute a major cause of death. Novel biological break- throughs such as the emergence of human induced pluripo- tent stem cells (iPSCs) and the generation of engineered cardi- ac tissue models offer immense potential for pharmaceutical RD as well as precision medicine. Current model systems, however, require large amounts of cells and rely on complex cell injection protocols, hampering the adoption of the tech- nologies and fulfillment of their promises. Screening of libraries requires the individual testing of sub- stances. In this project, a genetically encoded fragment-based platform technology from the company Hour Discovery is used for screening for peptides that bind to multiple TLRs. These phage libraries comprise more than 1 linear and cyclic peptides, which are screened simultaneously and in competi- tion to each other via cell-based TLR reporter gene assay (EP 1 1) and via a cell-free system at Fraunhofer IGB. Thus, TLR-binding peptides can be found in just one proce- dure and identified by phage coding using deep sequencing. Hit peptides are provided by EMC microcollections GmbH and their antagonistic effect is validated at the IGB via the cell-based reporter gene assay. These antagonists will be in- vestigated with human 3D in-vitro skin models complemented by TLR overexpressing reporter gene skin cells (EP 1A1) and psoriasis biopsies in topical application (Fig. ). We have developed a centrifugal heart-on-chip (HoC) plat- form with the potential to be a widely-applicable, user-friendly tool. The platform allows for a parallelized generation of car- diac -tissues, mimicking a minimal functional unit of the heart muscle. It is based on simple centrifugation steps utiliz- ing basic infrastructure present in all cell culture laboratories (Fig. ). The HoC provides a physiologically relevant in-vitro model which can be utilized for drug testing or disease mod- elling. In the next project stage, we will integrate read-out ca- pabilities for the in situ determination of contractile forces and electrophysiological parameters as well as introduce external stimuli to improve tissue maturation. All in all, the novel centrifugal HoC represents a fit-for-pur- pose system which can be used by any laboratory and tailored for each specific application. This downscaled physiological model system offers unprecedented opportunities in cardio- vascular research harnessing the true potential of iPSC tech- nology. www.igb.fraunhofer.de/en/psobibi www.igb.fraunhofer.de/en/heart-on-chip Contact Dr.-Ing. Christina Kohl Phone 11 -1 christina.kohl@igb.fraunhofer.de Contact Oliver Schneider Phone 11 -1 oliver.schneider@igb.fraunhofer.de 4 5

We combine BIOLOGY and ENGINEERING ... … by engineering viruses at the genome level. In this way, we can program tailor-made viruses and viral platform vectors for therapeutic use and produce them biotechnologically, for example to combat cancer. apl. Prof. Dr. Susanne Bailer … by culturing human tissue cells in an artificial, microphysiological environment. The functionality of the organs is reproduced in our organ-on- chip systems, as we demonstrate with beating heart or seeing retinal tissue, amongst other examples. This makes them suitable for non- clinical screening of pharmaceutical drugs, cosmetics and chemicals as well as for basic biomedical research and personalized medicine – leading to a reduction of animal testing. Jun.-Prof. Dr. Peter Loskill … by combining high-throughput DNA sequencing and bioinformatics. This enables innovative, novel diagnostic platforms – Next Generation Diagnostics. Dr. Kai Sohn 4 74 7

DEVELOPING AND SCALING UP PROCESSES FOR THE PRODUCTION OF SUSTAINABLE CHEMICALS, FUELS AND MATERIALS FROM BIOGENIC RAW / WASTE MATERIALS AND CO2 Target markets Fraunhofer IGB is a partner for industrial companies that produce, process or use chemicals, companies in machine and plant engineering and engineering companies. We focus on the following areas: Fine and specialty chemicals Given our enormous expertise in the field of interfacial engi- neering, we are particularly interested in product groups such as surfactants and coating systems. We also focus on the synthesis and characterization of substances and materials for which an interaction with biological systems plays an essential role. Examples here include additives for agriculture such as plant boosters made of microalgae, which positively impact cell growth in agricultural crops. Biopolymers and biobased polymers We also develop biopolymers for use as packaging for food- stuffs or for medicinal products (see Health business area). By using advanced coatings or the special functionality of bio- based monomers, we are able to create new properties for materials. Examples here include the transparent Caramid-R® polyamides that Fraunhofer IGB has developed from terpenes. Based on renewable materials such as sugar, rapeseed oil or algal lipids, we have also been able to demonstrate other bio- tech methods of synthesizing feedstocks for the production of plastics. Such raw materials include e.g. short- and long-chain dicarboxylic acids and fatty acid epoxides. Food, animal feed and cosmetics Given their antioxidant, immunostimulant or antimicrobial properties, functional ingredients made of microalgae can be used as animal feed or food supplements. The same is true of certain byproducts from the agricultural and food industries. For this purpose, we develop cultivation methods and product-friendly separation methods for extrac- tion and purification. In addition, we develop new physical processes to stabilize and preserve food, cosmetics, active ingredients and plant extracts. Power-to-X and chemical CO2 recycling The ready availability of renewable electrical energy means that the chemical and energy sectors will increasingly merge in the future. This is because the redox equivalents generated in power-to-x processes can be used for synthesis. Fraunhofer IGB is building the Electrolysis Test Platform ELP at the Fraunhofer location in Leuna and the Hy2Chem scale up platform for chemical synthesis with regenerative hydrogen so as to be able to depict – as in other areas – new technological developments right up to the demonstration scale. Modular plant engineering Various factors are driving the growth of modular plant engi- neering in the processing industry. These include increasingly shorter development and implementation timescales coupled with the need to increase the efficiency, adaptiv- ity and flexibility of processes and thereby achieve simple scalability to meet fluctuating demand. Given the wide range of engineering expertise available at Fraunhofer IGB, we have been able to incorporate aspects of modular plant engineering in our development of new processes right up to the demonstration scale – as already shown in the Fraunhofer consortium MODAB. Contact Dipl.-Chem. (FH) Gerd Unkelbach Phone 1 -11 gerd.unkelbach@cbp.fraunhofer.de 4 9

3 4 SurfGlyco – Improved strategies for the biotechnologi- BioDiMet – Selective sustainable methylation for a cal production of tailor-made biosurfactants diversity-oriented synthesis of bioactive substances Surfactants are surface-active molecules that are used in large quantities in numerous products. Market studies postulate a global annual consumption of up to 20 million tonnes by 1. In the cosmetics and personal care market, in particular, consumer awareness of the use of biobased products has increased. Therefore, companies have already established chemically synthesized surfactants based on renewable raw materials. However, the rather unsustainable production of most of the oils needed for their manufacture requires alternatives, which have been investigated in the SurfGlyco project. Fraunhofer IGB focused on the optimization of the microbial production of biosurfactants from sugars as the sole carbon source. After selecting microorganisms that synthesize so- called cellobiose lipids (CL), the fermentation process was optimized and transferred to a bioreactor system to provide CL samples for application tests conducted by the project partners. Beyond that, we established methods for product recovery that either use non-toxic solvents such as ethanol or do not use organic solvents at all. Our partners have made Development of a sustainable method for the synthesis of novel bioactives will help to meet demand in the various markets of the pharmaceutical, agrochemical and fragrance aroma industries. BioDiMet is an ERA CoBioTech project. Its objective is to develop a modular and robust methyltrans- ferase toolbox that can be used for the selective synthesis of novel bioactives for pharmaceutical applications. For this pur- pose, Fraunhofer IGB is developing chemoenzymatic cascade reactions involving S-adenosylmethionine (SAM)-dependent methyltransferases (MTs) combined with a cofactor supply sys- tem. This method of synthesis follows the biosynthesis strat- egy from nature and is therefore ideal for use in conjunction with biobased molecules. By contrast, the use of conventional synthetic methods of methylation is not particularly practi- cable under similar conditions. The BioDiMet project is being conducted by a leading global consortium comprising seven expert teams from five countries. This work comprises three technology platforms: the synthesis of novel methyl acceptors, the development of new methyltransferases and the provision of SAM analogues. progress in using CLs in indicative prototype formulations. The work opens up the possibility of using CLs as multifunctional additives in cosmetic or personal care products. This is due to their ability to disperse lipophilic and hydrophilic substances in oil and water. Furthermore, the CLs showed potential as emulsion stabilizer and thickener. This points to future broad To date, the project has demonstrated new reaction cascades, developed dozens of new methyltransferases, established a rapid analytic method for methylation reactions and synthe- sized novel methyl acceptor substrates for pharmaceutical applications. These various modules will now be combined in order to set up an exclusive methyltransferase toolbox for use applicability in formulations of various kinds. in industry. www.igb.fraunhofer.de/en/surfglyco www.igb.fraunhofer.de/en/biodimet Contact Dr.-Ing. Susanne Zibek Phone 11 -1 susanne.zibek@igb.fraunhofer.de Contact Dr. Michael Richter Phone 1 1- michael.richter@igb.fraunhofer.de 51

3 4 SusPackaging – Sustainable production of Functional ingredients from algae for health-promoting polyhydroxyalkanoates (PHA) for packaging materials food and as plant strengthening agent in viticulture Plastic pollution and accumulation of microplastics in the oceans are increasingly gaining public awareness and spurring the cosmetic and food industries on to meet the demand for environmentally responsible packaging concepts. Thus, SusPackaging aims to initiate a green value chain for the production of biodegradable, biobased packaging materials. Polyhydroxyalkanoates (PHA) are biodegradable biopolymers that have properties similar to conventional plastics. PHAs are naturally produced by bacteria as intracellular storage granules that serve as a source of carbon and energy and may comprise up to of the cell dry weight. Currently, high cost of production and downstream processing results in PHAs being uncompetitive compared to conventional oil-derived polymers. During this project, Fraunhofer IGB has evaluated the produc- tion of different PHA molecular variants through selection and isolation of microorganisms able to transform sustainable carbon sources like methane from the biogas production, sugars derived from cellulose and hemicellulose from forestry and agricultural residues, and glycerol resulting from biodiesel production. Additionally, a highly efficient, solvent-free down- stream processing approach is being developed. The use of pressure change technology (PCT) and supercritical fluids for cell disruption and material recovery has been adapted for this application (Fig. ). The physical-chemical properties of the materials obtained, correlation to key quality requirements, and a life cycle potential analysis are being studied in coopera- tion with our project partners. The MIATEST project deals with the production of functional ingredients from diatoms and their application in different areas. At Fraunhofer IGB, the production of the ingredients as well as their extraction and purification are optimized. In the field of microalgae cultivation, the cultivation conditions significantly influence the composition of the biomass. For example, the chrysolaminarin content can be increased from w / w to w / w by adjusting the cultivation conditions. Together with the State Research Institute for Viticulture and Fruit Growing, the application of chrysolaminarin as a plant strengthening agent in viticulture is being tested. The aim here is to find an alternative to existing copper-based fungi- cides against fungal diseases. The University of Hohenheim is carrying out experiments on the application of the micro- algae biomass in the field of human nutrition. Apart from chrysolaminarin, these experiments are mainly focused on the pigment fucoxanthin and eicosapentaenoic acid, an omega- fatty acid. Fucoxanthin, in particular, has led to considerable interest in the industry, as it shows antioxidant, anti-inflammatory, anti- cancer and weight-reducing properties. At Fraunhofer IGB, a process for obtaining highly pure fucoxanthin ( ) has already been developed in another project. www.igb.fraunhofer.de/en/suspackaging www.igb.fraunhofer.de/en/miatest Contact Dr. Ana Lucía Vásquez-Caicedo Phone 11 - analucia.vasquez@igb.fraunhofer.de Contact Konstantin Frick M. Sc. Phone 11 - konstantin.frick@igb.fraunhofer.de 5 3

3 4 CELBICON – Coupling electrochemistry and biotechnol- Synthesis of hydrogen peroxide in ogy to convert CO2 into value-added chemicals an electrochemical cell The development and deployment of processes to utilize the greenhouse gas carbon dioxide (CO2) will be a central build- ing block of a future climate-neutral and resource-efficient circular economy. Researchers from Fraunhofer IGB have developed and validated such a process chain in collaboration with partners from academia and industry in the course of the EU-funded project CELBICON. Adsorption of CO2 from air (direct air capture, DAC) is the first process step, achieved in a pilot plant provided by project partner Climeworks (Switzerland). The captured CO2 is then converted electrochemically into formic acid. For this step, Fraunhofer IGB has developed tin-based electrocatalysts and a phosphate-buffered electrolyte. Furthermore, Fraunhofer IGB has designed and constructed an automated demonstration plant (Fig. ) featuring an electrolytic cell from project partners Gaskatel (Germany) and Hysytech (Italy), in which the electro- chemical conversion of CO2 captured from air into formic acid could be tested in a relevant operational environment. In the CELBICON project it was also demonstrated that electrochem- ically generated formic acid can be applied as substrate in a fermentation process to yield a product from the terpenoid metabolism. A fed-batch process at 1 L scale has been devel- oped, enabling promising biomass yields based on optimized operational parameters. Product purification was successfully established, and it was demonstrated that 1 of the fed formic acid can be converted into a terpenoid dye. Hydrogen peroxide (H2O2) is an important chemical product. At present, of the worlds annual H2O2 production of about 2.2 million tonnes is based on the anthraquinone process – a costly method and impractical for routine on-site application at small scale. An alternate synthetic pathway is the electrosynthesis of H2O2, which is cost-efficient and applicable on both large and small scales. In collaboration with the University of Southampton, Fraunhofer IGB researchers recently published a review article describing various approaches to design and assess electrode materials for H2O2 electrosynthesis. One such approach is the partial reduction of oxygen (O2) at cathodes featuring either noble metal alloys or doped carbon. Alternatively, H2O2 can be prepared by oxidizing water (H2O), using efficient anodic catalysts based on metal oxides, such as BiVO, and other materials. The main challenge in the latter approach is to sup- press the thermodynamically favored oxygen evolution reac- tion. As part of the EU-funded CO2EIDE project, the task of Fraunhofer IGB and project partners is to develop active and selective catalysts for simultaneously synthesising ethylene (C2H) through cathodic reduction of CO2, and hydrogen per- oxide through anodic oxidation of water. Both products are used in a subsequent reaction step to generate ethylene oxide (C2HO). Thus, the CO2EIDE approach enables the efficient production of three important platform chemicals – ethylene, hydrogen peroxide, and ethylene oxide – from the educts CO2, water and electric energy, hence from abundant and entirely renewable resources (Fig. ). www.igb.fraunhofer.de/en/celbicon www.igb.fraunhofer.de/en/co2exide Contact Dr. Lénárd-István Csepei Phone 1 1- lenard-istvan.csepei@igb.fraunhofer.de Contact Dhananjai Pangotra M. Sc. Phone 1 1- dhananjai.pangotra@igb.fraunhofer.de 5 5

We combine BIOLOGY and ENGINEERING ... … by complementing the toolbox of chemical synthesis with a bioinspired approach. In doing so, we provide unique access to new biobased substances and materials that are suitable for a wide range of technological applications. Dr. Michael Richter … through the material use of biogenic, regenerative resources for the synthesis of chemicals. In doing so, we can map entire value-added chains from laboratory to pilot plant scale and create the prerequisites for implementing climate- friendly synthesis processes in industry. Ulrike Junghans … by cultivating microalgae with bioprocess engineering know-how in photobioreactors to produce complex biological substances. Due to their functional properties, they are suitable as valuable food supplements or can be used as pigments in cosmetics. Felix Derwenskus, Gordon Brinitzer, Dr. Ulrike Schmid-Staiger 5 75 7

SUSTAINABLE RESOURCE MANAGEMENT FOR INDUSTRY, MUNICIPAL AUTHORITIES AND AGRICULTURE Target markets Smart infrastructure for smart cities In particular, we focus on developments in the area of smart infrastructure. This requires a holistic consideration of all the aspects of municipal infrastructure, covering the areas of water, energy, food and waste. Fraunhofer IGB has many years of experience in integrated water management on the municipal and regional level, as well as in the use and development of new methods made available through the increasing digitalization of the water sector. This work focuses on the development of integrated strategies to help cities, towns and neighborhoods cope with heavy rainfall, drought and other extreme weather events caused by climate change. Production and treatment of drinking water Water vapor in the atmosphere is a source of high-quality drinking or process water. Current research at Fraunhofer IGB is focusing on the use of efficient adsorption systems that capture atmospheric water and, when required, release this as drinking water and other purposes. We have many years of expertise in the investigation of bacte- rial contamination and in the determination of the efficacy of individual disinfection approaches. We specialize in the identification of bacteria and fungi as well as in the analysis of biofilms and how to reduce or avoid them in technical systems. Treatment of process water, wastewater and sludge Based on our many years of experience in this field, Fraunhofer IGB offers both biological and physico-chemical methods and solutions for wastewater treatment and sludge conditioning for industry and municipalities. Our portfolio also includes customized membranes, filters and adsorbents, which will play important roles in the growing future markets for water and wastewater treatment systems. Water monitoring A further important activity at Fraunhofer IGB is the devel- opment of sensors and monitoring systems for use in measuring and assessing harmful substances in the soil and in water. We have key expertise in the biological components of biosensors, the functionalization of sensor surfaces, analytics, automation and data analysis. Biogas As one key source of regenerative and dispatchable energy, biogas is a key enabler in the transition towards a sustainable energy system. This is also because biogas can be stored for a long period of time, which means it can be used to generate power according to demand. Our method of high-load digestion for the efficient production of biogas from sewage sludge has already been implemented at a number of municipal wastewater treatment plants. We also develop specific solutions for the conversion of biowaste to energy. These range from fermentation tests to the design of plants on a technical scale and the optimization of agricultural biogas plants in terms of productivity and efficiency. Secondary resources, raw materials and water reuse With its developments in biotech and physico-chemical processes for recovering valuable materials and nutri- ents (P, N) from sewage and other sources of waste as well as for the reuse of treated wastewater, Fraunhofer IGB makes important contributions towards the establishment of a sustainable bioeconomy inspired by the natural cycles of materials. One example is our ePhos® system, an electrochem- ical process for the recovery of phosphorus from wastewaters rich in phosphates. Its efficiency has been demonstrated at the pilot plant scale. Contact Dr.-Ing. Ursula Schließmann Phone 11 - ursula.schliessmann@igb.fraunhofer.de 5 9

3 4 Process control of blue-green infrastructures in Leipzig Water reuse in agriculture – HypoWave project successfully completed Leipzig is a growing metropolis; the development of further residential areas in the city center is therefore an important goal of urban development. However, structural redensifica- tion and the consequences of climate change (heat, heavy rainfall) place an enormous burden on the water and energy infrastructure. The citys parties involved are thus confronted with new planning and legal issues. The BMBF-funded joint project Leipzig Blue-Green – Blue- Green uarter Development in Leipzig is intended to show, using the example of the large-scale project Eutritzscher Freiladebahnhof (Eutritzsch Free Loading Station), how a runoff-free and resource-efficient urban quarter can be de- signed. Blue stands for water, green for plants as an element of urban infrastructure. The aim is to develop new, transfer- able blue-green technologies and planning tools as well as a sensor-based, robust process control. Fraunhofer IGB is investigating how the combination of blue-green technologies can be controlled equally robustly and efficiently and how the operation and maintenance of the system architecture can be ensured sustainably. In this context, the IGBs experience in process automation and han- dling of measurement data can be transferred to the urban district level. In a first step, elements such as green roofs will be automated on the campus of the Helmholtz Center for Environmental Research Leipzig, e.g. by controlling the runoff based on weather forecasts. The results are then transferred to the planned quarter. Since 1, Fraunhofer IGB has been involved in the joint research project HypoWave, which investigates the extent to which treated municipal wastewater can be used in hy- droponic plant cultivation for the production of high-quality vegetables or cut flowers. The developed processes have been piloted on a sewage treatment plant in Wolfsburg (Fig. ) over three vegetation periods. In addition, various replication and implementation options have been analyzed and developed in case studies involving local stakeholders in Belgium, Por- tugal, Northern and Central Germany. In 1, the results of Hypowave were shared with the professional community at several events. With the use of treated wastewater, two objectives can be achieved: the purification of wastewater, especially regarding nitrogen and phosphorus elimination, and optimal plant growth through good water and nutrient supply. Adequate quality management is necessary to ensure a good supply of micronutrients to the plants and to comply with microbiological hygiene requirements. For example, ir- rigation water should be sanitized using suitable disinfection measures, e.g. UV, ozone or membrane filtration. Opportunity windows for the implementation of the HypoWave concept are situations in rural areas susceptible to water scarcity and where the wastewater infrastructure has to be adapted or (re)developed. Water reuse can also be integrated into waste- water treatment plants that are planning a fourth treatment stage, and is suitable in principle for city expansions and new district buildings. In this way, conflicts over the use of water resources, which are becoming more acute due to climate change and overexploitation, can be defused. www.igb.fraunhofer.de/en/leipzigerblaugruen www.igb.fraunhofer.de/en/hypowave Contact Dipl.-Ing. Christiane Chaumette Phone 11 -11 christiane.chaumette@igb.fraunhofer.de Contact Dr.-Ing. Marius Mohr Phone 11 -1 marius.mohr@igb.fraunhofer.de 61

We combine BIOLOGY and ENGINEERING ... ... through the use of microorganisms for the purification of wastewater. To this end, we develop efficient bio- engineering processes and combine them with a holistic understanding of systems, such as production processes and urban systems. In this way, we utilize wastewater and waste streams as resources – for generating purified water, energy and nutrients. Dr.-Ing. Marius Mohr … by assessing the hygiene status of technical surfaces or antimicrobial material surfaces with standardized microbiological assessment methods. Bryan Lotz … by optimizing the efficiency of biogas plants – i.e. the productivity of biogas- producing micro- organisms – through process engineering. Dr. Brigitte Kempter-Regel 6 36 3

INNOVATION FIELDS FRAUNHOFER-GESELLSCHAFT Research of practical utility lies at the heart of all activities pursued by the Fraunhofer-Gesellschaft. Founded in 1, the research organization undertakes applied research that drives economic development and serves the wider benefit of society. Its services are solicited by customers and contractual partners in industry, the service sector and public administra- tion. At present, the Fraunhofer-Gesellschaft maintains institutes and research units. The majority of the more than , staff are qualified scientists and engineers, who work with an annual research budget of more than . billion euros. Of this sum, more than . billion euros is generated through contract research. Around percent of the Fraunhofer- Gesellschaft’s contract research revenue is derived from con- tracts with industry and from publicly financed research proj- ects. Around percent is contributed by the German federal and state governments in the form of base funding, enabling 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. 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. With its clearly defined mission of application-oriented re- search and its focus on key technologies of relevance to the 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 region, and throughout Germany and Europe. They do so by promoting innovation, strengthening the technological base, improving the acceptance of new technologies, and helping to train the urgently needed future generation of scientists and engineers. 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 within their institute, at universities, in industry and in society. 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 experience they have acquired. The Fraunhofer-Gesellschaft is a recognized non-profit or- ganization that takes its name from Joseph von Fraunhofer (1 – 1), the illustrious Munich researcher, inventor and entrepreneur. Figures are for January . www.fraunhofer.de Fraunhofer headquarters in Munich, Germany. 6 5

Virus-based technologies Functional ingredients The focus of this innovation field is on concepts and solutions for the use of viruses and phages for the targeted medical (prevention, therapy, diagnostics) or biotechnological applica- tion and biointelligent use. The services offered range from genome engineering to process development for the produc- tion of viral agents in lab-scale. One focus is the development of viruses into therapeutic agents. Oncolytic viruses, for example, represent promising and innovative cancer therapies. In the innovation field, a viral platform based on Herpes Simplex Virus 1 (HSV-1) has already been developed. The ability of viruses/viral vectors to trans- port genetic information into cells and anchor it there can be used in diverse ways, e.g. for cell and gene therapy. Bacteriophages are attractive alternatives for combating anti- biotic-resistant bacteria and can be used in a variety of tech- nological ways, for example for the production of antibodies, as biointelligent actuators and sensors in fermentation or for the degradation of biofilms. In addition, within the innovation field we are developing virus-like particles as vaccines and for targeted drug delivery. Fields of activity and technologies Engineering of therapeutic viruses Oncolytic viruses Viral vectors (Cell and gene therapy) Phage technology Virus-like particles The innovation field focuses on the customized production and processing of functional ingredients from microalgae and bacteria for the production of food and feed, cosmetics, biostimulants and biobased polymers. Processes based on CO2, methane and renewable resources are being developed for this purpose. By means of targeted process management, these processes can be transferred to pilot scale. For faster process development, new online analysis methods (real-time MS) and predictive models for control systems are used. Furthermore, the focus is on processing technologies, such as the efficient extraction of carotenoids and omega- fatty acids with subcritical solvents and recovery of the individual components. New non-thermal processing methods (pas- teurization and cell disruption) are used to obtain high-quality ingredients in food and contribute to a healthy diet. Thermal treatment (dryingtorrefaction) of material flows with super- heated steam and integration into a value-added chain will allow them to be processed more efficiently. Energy-efficient processes for the extraction of drinking and process water from air are designed for technical implementation. Fields of activity and technologies Process development for customized algae ingredients Cell disruption and extraction with subcritical fluids Pressure change technology (PCT) for food Drying / torrefaction with superheated steam Sorptive water extraction from air Gas fermentation with methane Real-time fermentation analysis with MS Contact apl. Prof. Dr. Susanne M. Bailer Phone 11 -1 susanne.bailer@igb.fraunhofer.de Contact Dr. Ulrike Schmid-Staiger Phone 11 -111 ulrike.schmid-staiger@igb.fraunhofer.de 6 7

Functional surfaces and materials Regenerative resources The design of material and product surfaces to achieve de- fined target properties is in demand for many applications in the automotive industry, medical technology and diagnostics, textiles and packaging, etc. This innovation field gives surfaces of plastics, ceramics or metals new properties and offers solutions for applications that require a combination of dif- ferent processes. In sensor coating, for example, the chemical modification of coating materials is combined with printing and plasma processes to apply functional layers. In this innovation field, for the modification of surfaces we use and develop plasma processes from laboratory to roll-to- roll pilot scale, as well as coating processes from the gas and liquid phase. For material production, we have expertise in chemical synthesis and formulation. The innovation field has comprehensive analytical equipment for the characterization of surfaces, polymers and particles – for process control, qual- ity assurance and damage analysis. Fields of activity and technologies Materials and formulations ¡ Modification of biopolymershydrogels ¡ Encapsulation/particulate systems ¡ Ink formulation for bioprinting ¡ Formulation of coating dispersions Functional surfaces ¡ (Bio)sensor surfaces ¡ Anti-iceanti-adhesion coating ¡ Coatings for medical technology ¡ Barrier coatings The innovation field of regenerative resources in the two working groups Biomass Fractionation and Chemical Pro- cesses deals with the development of innovative procedures and processes for the material use of regenerative resources (lignocelluloses, carbohydrates, oilseed, protein fractions, CO2) for the production of renewable chemicals. Biogas and syngas also play an increasingly important role. With the existing know-how, a wide range of process steps for the develop- ment of processes from the laboratory (TRL – ) to the pilot plant scale (TRL ) can be covered. This combines processes to investigate complete value chains from raw material supply and conditioning to the isolation of material flows and its chemical transformation as well as implemented processes for effective product separation and purification. Sample quantities from kilogram to ton scale can be provided. The techno-economic evaluation of the processes plays a decisive role in the implementation in biorefinery concepts. Together with partners, we conduct assessments that serve as the basis for further process and plant design on a demonstration or industrial scale. Fields of activity and technologies Biomass fractionation ¡ Oilseed biorefinery ¡ Lignocellulose biorefinery Chemical processes ¡ Biogenic epoxy resins ¡ Added value of lignin ¡ Electricity-based fuels and chemicals – Leuna electrolysis platform ¡ Product separation and processing ¡ Process and plant design Contact Dr. Michaela Müller Phone 11 -1 michaela.mueller@igb.fraunhofer.de Contact Ulrike Junghans M. Sc. Phone 1 1 ulrike.junghans@cbp.fraunhofer.de 6 9

Bioinspired chemistry This innovation field researches sustainable conversion pro- cesses and is particularly concerned with the development of new synthesis and production methods for fine and specialty chemicals and for functional materials of the future. In doing so, we use biomolecular structures and synthesis principles to create new material properties. The innovation field focuses on interdisciplinary approaches to synthetic and retrosynthetic strategies that combine chemical and biological aspects and thus lead to innovative manufac- turing processes. The functionality of the products is evalu- ated on the basis of application requirements and optimized with regard to industrial use. The aim of our activities is to expand the toolbox for sus- tainable synthesis by synopsis of raw materials, conversion methods and desired product properties. Thereby we want to achieve technological leaps towards green chemicals and novel functional materials. Fields of activity and technologies Development of bioinspired synthesis routes Chemo-enzymatic synthesis Organic synthesis Biobased monomer and polymer synthesis Production and processing of biobased materials Transient, responsive, switchable materials Biodegradation of specialty chemicals Chemical analysis, material characterization and material testing Contact Dr. Michael Richter Phone 1 1- michael.richter@igb.fraunhofer.de 7 1

EDITORIAL NOTES EDITORIAL TEAM Dipl.-Wirt.-Ing. (FH) Antje Hetebrüg, Jan Müller M. A., Dipl.-Des. Thaya Schroeder (picture), Dr. Claudia Vorbeck and the scientists referred to as authors or contact persons. LAYOUT AND PRODUCTION Dipl.-Des. Thaya Schroeder PRINTING Fraunhofer Verlag, Media Services, Stuttgart, Germany EDITORIAL ADDRESS Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB Dr. Claudia Vorbeck Nobelstrae 1, Stuttgart, Germany TRANSLATIONS, PROOFREADING Dr. Stuart Amor, Stuttgart, Germany Beckett Translations, CV N, Long Compton, UK Textworks Translations, Manchester, UK Dr. Sabine Wacker Wacker Translation, Aichwald, Germany PHOTO ACKNOWLEDGMENTS Bayerl, Günther: pages , 1, Fogel, Walter: page Kleinbach, Frank: page Krötz, Rafael: page Michalke, Norbert: cover, pages , Müller, Bernd: cover, pages , , , , ökonzept: page Shutterstock: cover, pages 1, 1, , , 1, , , All other photographs and figures Fraunhofer IGB Fraunhofer-Gesellschaft This annual report was printed climate-neutrally with inks based on vegetable oil. The paper used is 1 recycled and the raw materials come from sustainable forestry. It is awarded the EU Ecolabel AT 11 and the Blue Angel. BioEcoSIM®, Caramid-R®, Caramid-S®, ePhos , NANOCTES®, nanodyn®, Morgenstadt® and POLO® are registered trademarks of the Fraunhofer- Gesellschaft zur Förderung der angewandten Forschung e. V., München, Germany. Reproduction of any material requires the editors’ consent. Fraunhofer IGB, Stuttgart 7 3

100 Committee memberships 258 Projects 119 Strategic cooperations 33 Newly granted patents Detailed information www.igb.fraunhofer.de/data