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Improving biotech production with real-time testing

Marieke Klijn detects changes in biotechnological processes in real-time, with the use of new monitoring techniques. She wants to move biotechnological research away from old-fashioned manual sampling to much more efficient continuous testing: “We can now know at once how many cells are alive during the production process, or how fast they are eating glucose, for example – all without the need to take a sample.” “My research focusses on ways to optimize production processes for biotech companies, by developing methods for continuous testing,” Marieke Klijn, assistant professor at the biotechnology department of the TU Delft, begins. “My team aims to make measurements an automatic part of production processes in biotechnology. I want to integrate sampling directly into the process – real-time testing: that way, we no longer need to rely on time-consuming manual handling in order to know how well the production process is going.” She set up her lab at TU Delft in September 2020. Read more Higher quality and more sustainable Klijn explains that continuous testing will lead to biotechnological products with higher quality and processing efficiency: “Real-time testing improves product quality, because the biotech company has continuous control of the product: the computer can easily detect deviations in the production chain at a much faster pace and change parameters so as to prevent failure, like a loss of product or unhappy cells. Real-time testing is also required if you want to move to continuous manufacturing, which allows companies to reduce their footprint and become more sustainable.” The biopharmaceutical industry is actively searching for more continuous processing setups that can lead to more efficient and affordable production of medicine, such as vaccines or cancer medicine. Klijn: “A continuous process flow already exists in other types of industries, such as the petrol industry. But in the case of biological matter, continuous processing and testing is more difficult: it has more technological, biological and regulatory challenges. You can’t be sure of the result in advance.” Eating habits of cells in real-time “In my lab we have a setup to insert analytical techniques into a bioreactor and extract processing data in real-time,” Klijn explains. “A bioreactor is basically a vessel with nutrients and cells. These cells can produce a specific biotechnological product, for example a food additive or a drug compound, in a highly controlled environment. We would like to monitor different cells to find out how to make these models robust for industrial application: so that when products or cell lines change, the company doesn’t need to go through the whole development phase again.” The main analytical tool that Klijn’s lab uses is Raman spectroscopy: a technique in which laser light is scattered due to molecular vibrations. Each molecule will have a different scattering pattern, making it possible to study all kinds of changes in different molecules in real-time: “With this technique we now know at once how many cells are alive during the production process, or how fast they are eating glucose, for example – all without the need to take a sample. The combination of this analytical technique and machine learning makes it possible to look at many different parameters at the same time.” The main analytical tool that Marieke Klijn uses is Raman spectroscopy, a technique in which laser light is scattered due to molecular vibrations. Blurry lines The biotechnological industry already makes use of Raman spectroscopy: they show a lot of interest in the models that the team can build for the process control systems. “We would like to capture as much information as feasible. For example, in addition to Raman spectroscopy, we want to use real-time imaging data to tell us how the cells are changing during the process of glucose eating.” The sheer amount of data this entails presents a challenge in itself, Klijn says: “Our dilemma here is how to effectively use the huge amount of information that we acquire.” How has this new focus on improvements during bio-production influenced the research field? “Before I started this work, each specialist would focus on their own part of the manufacturing process. Now the lines are blurry and they all work together. This makes the work very diverse. I can combine implementation of data analytical tools, with how the cell works and bioprocess engineering solutions. I work with experts from many different fields on the upstream part of processing, such as cell cultivation, and the downstream part such as modellers: all to make the production process into one single continuous flow.” Dr. ir. Marieke Klijn Assistant Professor +31 15 27 81280 m.e.klijn@tudelft.nl Room C0.550 Building 58 Van der Maasweg 9 2629 HZ Delft linkedin More stories

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Three Students Nominated for the ECHO award

Three TU Delft students have been nominated for the ECHO Award 2024. The ECHO award is awarded to students with a non-western background who are actively engaged in society. Sibel, TJ and Pravesha talk about their background their nomination. The finalists will be selected on September 27th. Sibel Gökbekir How has your background influenced your academic journey? As a woman with Turkish roots, my academic journey has been about more than just pursuing degrees in engineering and law; it’s been about consistently advocating for the diverse needs of women and multicultural groups, ensuring their voices are heard in important decisions. This is why I actively contributed to different board positions at TU Delft, working to promote inclusivity and equality. My background inspired me to explore how engineering, law, and social justice intersect, particularly in empowering marginalised communities. I chose to study energy transitions and human rights to contribute to a fairer, more inclusive World. How have you turned this into contributions to society? I’ve dedicated my academic and personal life to promoting diversity and inclusion. As a youth ambassador for Stop Street Harassment, I aimed to create safer spaces for women and minorities because I believe everyone has the right to feel free and safe in society. Through the Turkish Golden Tulip Foundation, I advocated for vulnerable communities in earthquake relief. Additionally, I founded an initiative for migrant students in Rotterdam-South and I have been committed to improving educational opportunities for secondary school students with a migration background. Next, I gave guest lectures across the Netherlands to educate the younger generation about climate change and equitable energy transitions, emphasising the importance of a fair transition for all communities. What does it mean for you to nominated to the ECHO award? I feel very honoured to have been nominated on behalf of TU Delft. My commitment to community engagement is part of who I am, and therefore the ECHO Award is more than just a recognition; It offers me an opportunity to further expand my contributions to a more inclusive society. As an ECHO Ambassador, I plan to expand my efforts in promoting equality and sustainability, while inspiring others to take action for a more equitable World. TJ Rivera How has your background influenced your academic journey? My background as a Filipino in a Dutch-speaking bachelor’s programme made my academic journey both challenging and enriching. Being gay in a male-dominated field like Architecture, where most role models were heteronormative men, added another layer of difficulty. It was intimidating to not see people like me represented. However, this experience fuelled my belief that systems can and should be challenged, changed, and updated. I aimed to bring a fresh perspective, advocating for greater diversity and inclusivity in the field. How have you turned this into contributions to society? I translated my personal challenges into tangible contributions by advocating for inclusivity within architecture. Together with like-minded individuals, I began exploring the intersection of identity, sexuality, and architecture, and collaborated with my faculty’s diversity team to raise awareness. As I became known for my work with the queer community, I saw an opportunity to create lasting change. I co-revived ARGUS, the once-inactive study association for the Master of Architecture, which now serves as a platform to discuss and address issues of diversity within the field. This initiative continues to foster a more inclusive academic environment. What does it mean for you to be nominated to the Echo award? Being nominated for the ECHO Award is a significant milestone in my journey to expand my mission beyond the confines of my faculty. This national platform provides the opportunity to raise awareness and advocate for social justice on a larger scale. I believe students are key to driving change, and my focus is on amplifying the voices of the queer community, which is often overlooked. The ECHO Award will enable me to form partnerships with organizations and universities, further promoting diversity, inclusivity, and equality. It’s a chance to create broader, tangible change, addressing the needs of those who often go unheard. Pravesha Ramsundersingh How has your background influenced your academic journey? As a woman in STEM (Science, Technology, Engineering, and Mathematics), my background has been a powerful motivator to challenge gender disparities within Computer Science. Experiencing firsthand the underrepresentation of women in this field, I have been driven to not only excel academically but also become an advocate for diversity. Through leadership roles in the Faculty and Central Student Councils, I’ve focused on creating an inclusive environment that supports women and minority students, ensuring that everyone has the opportunity to succeed. How have you turned this into contributions to society? I’ve translated my experiences into actionable contributions by actively advocating for DEI at TU Delft. I ensured sexual education and consent training for 3,000 freshmen students, and I led initiatives like the Social Safety Initiatives Conference alongside the Dutch National Coordinator against Racism and Discrimination. In my student governance roles, I pushed for policies that address gender discrimination and social safety concerns, creating a more supportive environment for students of all backgrounds to thrive in both academic and social spaces. What does it mean for you to nominated to the ECHO award? Being nominated for the ECHO Award is an incredible honour that highlights the importance of the work I have done to promote DEI. It inspires me to continue advocating for systemic change in the tech industry and academia. This nomination reaffirms my commitment to driving equity in STEM, ensuring that future generations have more inclusive opportunities. It also motivates me to keep pushing boundaries and empower others to take action for a more just and equal society. The ECHO Award Every year ECHO, Center for Diversity Policy, invites colleges and universities to nominate socially active students who make a difference in the field of Diversity & Inclusion for the ECHO Award 2024. The ECHO Award calls attention to the specific experiences that students with a non-Western background* carry with them and the way they manage to turn these experiences into a constructive contribution to society. Winners are selected by an independent jury and may attend a full-service Summercourse at UCLA in the United States in 2025. Read more: ECHO Award - ECHO (echo-net.nl)

NWO grants funding for innovative research on physical experimental environments

How to move from experiment to mainstream? A consortium led by professor Tamara Metze, has been awarded a prestigious grant from the Netherlands Organisation for Scientific Research (NWO). In search for pathways toward more sustainable futures, Metze and her team will explore how various innovations in field labs such as The Green Village, in urban living labs such as Engy Lab South-East in Amsterdam, and in all sorts of citizens’ initiatives, can be mainstreamed and make more impact on sustainability transitions. Pilot paradox The project ‘From EXperiment to sustainable change: TRAnsformative methodologies for Innovation and learning’ (EXTRA) seeks to overcome a persistent “pilot paradox”. In this paradox, much experimentation takes place but long-term systemic impact remains difficult. Researchers together with all sorts of change makers will synthesise existing knowledge on how to mainstream, upscale, spread, broaden and deepen developed innovations. Tamara Metze: ‘I am excited to unravel what are effective ways of cocreation that lead to mainstreaming the positive changes made in experimental environments. We will figure out how learning and innovation can lead to lasting changes in regulations, policies, and financial systems and the biophysical environment.’ Tamara Metze Read the NWO press release Actionable tools The project is crucial for accelerating sustainability transitions. By refining methodologies for mission-driven experimentation and develop hands on tools for all sorts of change-makers, it will be easier to mainstream the sustainable lessons and innovations. ‘These tools will not only aid grassroots innovators but also influence institutional and organisational structures, ensuring that lessons learned from experiments are better anchored in policies, regulations, and organisations’, explains Metze. The project will employ a transdisciplinary action research approach, bringing together knowledge from various disciplines and policy domains. By co-creating solutions with public and private partners, the research will have an immediate impact. In the long term, the project aims to build a more efficient innovation ecosystem, contributing to more impactful and sustainable outcomes for both society and the environment. Projectpartners TU Delft, VU Amsterdam, Wageningen University & Research, Hogeschool van Amsterdam, Erasmus Universiteit Rotterdam, Hogeschool Rotterdam, The Green Village, AMS Institute; PBL Planbureau voor de Leefomgeving, WoonFriesland, Dijkstra Draisma, Provincie Noord-Holland, Ministerie van Binnenlandse Zaken, PRICE / Almere, BouwLab, Alliantie Samen Nieuw-West, Innovation Quarter.

Unusual waves grow way beyond known limits

Waves that come from multiple directions are extremer than extreme. These remarkable deep-sea waves can be four times steeper than what was previously imagined, as is shown in research by TU Delft and other universities that was published in Nature today. A long time ago, stories were told of mysterious rogue waves that materialised out of nowhere and could topple even the largest ships. These waves lost their mythical character when the first rogue wave was recorded at the Draupner platform in the North Sea. In 2018, Ton van den Bremer and his colleagues at the Universities of Edinburgh and Oxford managed to recreate the Draupner wave in the lab for the first time ever, and this opportunity to study freak waves closely produced unexpected insights. Multiple waves push up water New research by the research consortium now shows that these remarkable waves do not break when traditional theories hold they should, the secret behind which lies in how they arise. Ton van den Bremer, expert on fluid mechanics at TU Delft and led the study, explains: “When most people think of waves, they think of the rolling waves you’d find on a beach. The type of wave we studied occurs in open water and arises when waves coming from multiple directions come together. When these waves with a high directional spread converge, the water is pushed upwards, forming a partially standing wave. An example of this is known as a crossing wave. How crossing waves arise Under certain conditions at sea, waves from multiple directions occur. This can happen in a place where two seas meet, or where winds suddenly change direction, as in a hurricane. When waves from two directions meet, a cross wave occurs, provided their directions are far enough apart. The study also shows that the further apart the directions are, the higher the resulting cross-wave. Travelling waves break when they reach a certain limit, this is when they reach their maximum steepness. The study shows that waves with a multidirectional spreading can get as much as 80% steeper than this limit before they start breaking, which means they can get almost twice as high as ‘normal waves’ before they start to break. Travelling wave (l) and a wave with high directional spreading (r) Breaking waves that grow Next, the researchers found another highly unusual phenomenon that defies existing theories, a phenomenon that is unprecedented according to Van den Bremer: “Once a conventional wave breaks, it forms a white cap, and there is no way back. But when a wave with a high directional spreading breaks, it can keep growing.” The study shows that these enormous waves can grow to twice their original steepness while breaking, which is already twice bigger than the conventional limit. Together, the waves can grow four times steeper than previously thought possible. Damage to offshore structures The knowledge that multidirectional waves can become as much as four times larger than was deemed possible can help design safer marine structures. "The three-dimensionality of waves is often overlooked in the design of offshore wind turbines and other structures in general; our findings suggest this leads to designs that are less reliable", says Mark McAllister of the University of Oxford, who led the experiments and is now a senior scientist at Wood Thilsted. Innovative vertical sensors made it possible to take accurate 3D measurements of waves. Innovative 3D measurement method A 3D measurement method developed in the FloWave lab paved the way for these new insights. “Conventional 2D wave measurement methods weren’t up to the task”, Van den Bremer explains, which is why the research group designed a new way to create 3D wave measurements. Ross Calvert of the University of Edinburgh: “This is the first time we've been able to measure wave heights at such high spatial resolution over such a big area, giving us a much more detailed understanding of complex wave breaking behaviour." FloWave Ocean Energy Research Facility in Edinburgh. The circular basin has a diameter of 25 metres and can be used to generate waves from multiple directions. Header image by: Fabien Duboc