PhD position: computational analysis of stem cell production in bioreactors

Stem cell therapies hold great promise when it comes to curing blood diseases - will your process insights ensure we can culture enough cells to make these therapies reality?

Blood is essential for oxygen transport, wound healing, and defence against pathogens. Short-lived mature blood cells are constantly replenished by hematopoietic stem cells (HSCs) throughout life. For many blood-related ailments, blood transfusion is often the only therapeutic option, and stem cell transplantation the only curative treatment for severe anemias. Unfortunately, a lack of immune-matched cells often hampers these therapies.

The TRACER consortium works on studying disease mechanisms as well as the production of mature bloodcells/HSCs from gene-corrected induced pluripotent stem-cells for therapeutic purposes. The team at TU Delft will focus on development of bioreactor technology for reliable high-density, low cost stem cell production for blood transfusion and curative applications. The team will consist of two PhD students, of which the current vacancy focuses on process modeling and simulation, whereas the prospective colleague will work on experimental cultivation and process monitoring/control. Within this project, you will actively work together with all partners, particularly Dutch blood bank Sanquin and Getinge-Applikon for bioreactor/process development.

PhD Project description:

The main objective of the process simulation project is to gain detailed insights in the cultivation environment, particularly conisdering gas-to-liquid mass transfer, mixing, hydrodynamic stresses and agglomeration using computational fluid dynamics.

Key focus points:

• Provide mechanistic insights into experimental observations related to HSC cultivation.
• Study integration of cellular response models with hydrodynamic models for cell culture applications.
• Provide input for experimental design choices.
• Design of robust cultivation protocols at various scales, from shake flask to fermentor, eventually leading to a production protocol for the manufacturing of blood cells/HSCs for therapeutic applications.

Several reactor configurations and scales, from shakeflask to production reactor, will be considered. The obtained insights will be use to further push the limits of the cultivation to obtaining higher cell numbers per unit volume. The CFD simulations will be used to inform process monitoring and control strategies. Insights obtained from the experimental work (ideally, including metabolic/proteomic models) will be included in the simulations. Additionally, there is room to explore the combination of hybrid mechanistic/data-driven modeling in the scope of bioprocess modeling.

Research group:

The project will take place in the Process simulation & Hydrodynamics group of the section Bioprocess Engineering at the department of Biotechnology. Our main objective is to study bioprocesses from the cellular point of view; how can we study interaction between cells and their environment, how does this affect process performance and how can we use the acquired knowledge to design better bioprocesses?

We are looking for a candidate that is self-driving and that can act as the manager of their own project. A strong background in process technology and an affinity for process simulation is desired. Considering the broad, multi-disciplinary nature of the consortium, we are looking for candidates that can effectively communicate their methods and results to stakeholders of various backgrounds, including non-technical.

• The ideal candidate holds an MSc (or equivalent) degree in biochemical engineering, chemical engineering, applied physics or a comparable program.
• A good academic track record is required, particularly in courses related to (bio)process engineering, transport phenomena and numerical techniques.
• Affinity for numerical analysis is necessary.
• Programming experience is strongly desired, ideally in Python or Julia.
• Experience with biomedical processes and (mammalian/human) cell biology is an advantage, but not essential.
• Fluent in English (written and spoken)
• Excellent communication skills and presentation capabilities, including communication with non-technical stakeholders. 

Doing a PhD at TU Delft requires English proficiency at a certain level to ensure that the candidate is able to communicate and interact well, participate in English-taught Doctoral Education courses, and write scientific articles and a final thesis. For more details please check the Graduate Schools Admission Requirements .

Doctoral candidates will be offered a 4-year period of employment in principle, but in the form of 2 employment contracts. An initial 1,5 year contract with an official go/no go progress assessment within 15 months. Followed by an additional contract for the remaining 2,5 years assuming everything goes well and performance requirements are met.

Salary and benefits are in accordance with the Collective Labour Agreement for Dutch Universities, increasing from € 2443 per month in the first year to € 3122 in the fourth year. As a PhD candidate you will be enrolled in the TU Delft Graduate School. The TU Delft Graduate School provides an inspiring research environment with an excellent team of supervisors, academic staff and a mentor. The Doctoral Education Programme is aimed at developing your transferable, discipline-related and research skills.

The TU Delft offers a customisable compensation package, discounts on health insurance and sport memberships, and a monthly work costs contribution. Flexible work schedules can be arranged. For international applicants we offer the Coming to Delft Service and Partner Career Advice to assist you with your relocation.

Delft University of Technology is built on strong foundations. As creators of the world-famous Dutch waterworks and pioneers in biotech, TU Delft is a top international university combining science, engineering and design. It delivers world class results in education, research and innovation to address challenges in the areas of energy, climate, mobility, health and digital society. For generations, our engineers have proven to be entrepreneurial problem-solvers, both in business and in a social context. At TU Delft we embrace diversity and aim to be as inclusive as possible (see our Code of Conduct ). Together, we imagine, invent and create solutions using technology to have a positive impact on a global scale.

Challenge. Change. Impact! 

With more than 1,000 employees, including 135 pioneering principal investigators, as well as a population of about 3,400 passionate students, the Faculty of Applied Sciences is an inspiring scientific ecosystem. Focusing on key enabling technologies, such as quantum- and nanotechnology, photonics, biotechnology, synthetic biology and materials for energy storage and conversion, our faculty aims to provide solutions to important problems of the 21st century. To that end, we train students in broad Bachelor's and specialist Master's programmes with a strong research component. Our scientists conduct ground-breaking fundamental and applied research in the fields of Life and Health Science & Technology, Nanoscience, Chemical Engineering, Radiation Science & Technology, and Engineering Physics. We are also training the next generation of high school teachers and science communicators.

Click here to go to the website of the Faculty of Applied Sciences.

Department of Biotechnology

Innovation is crucial to fulfil the potential of industrial biotechnology for sustainable production of fuels, chemicals, materials, food and feed. Similarly, scientific and technological advances in environmental biotechnology are needed to enable novel approaches to water purification, and ‘waste-to-product’ processes thus contributing to a circular economy. Increased fundamental knowledge encompassing enzymes, microorganisms and processes are essential for progress in this field. The Department of Biotechnology covers this research area and, based on new insights, selects, designs and tests new biobased catalysts, micro-organisms, and processes.

The position is available in the section Bioprocess Engineering

Are you interested in this vacancy? Please apply before 25 June 2022 via the application button and upload only your motivation letter and CV.

• A pre-employment screening can be part of the selection procedure.
• Applying for an exemption for specific research and educational areas is an obligatory part of the selection procedure for this vacancy. This exemption must be obtained from the Ministry of Education, Culture and Science (OCW) before an employment contract is agreed upon. Click here for more information.
• You can apply online. We will not process applications sent by email and/or post.
• Acquisition in response to this vacancy is not appreciated.

Only for more information about this vacancy, please contact Dr. ir. Cees Haringa, Assistant Professor Bioprocess Engineering, per e-mail [email protected]

Only for more information about the application procedure, please contact Ms. Kawieta Ramautar, Management Assistant, per e-mail [email protected]

* It is our aim to have the interviews in July 5, 8 or 12 and to fulfil the position preferably in August or September 2022.

Stem cell therapies hold great promise when it comes to curing blood diseases - will your process insights ensure we can culture enough cells to make these therapies reality?

Blood is essential for oxygen transport, wound healing, and defence against pathogens. Short-lived mature blood cells are constantly replenished by hematopoietic stem cells (HSCs) throughout life. For many blood-related ailments, blood transfusion is often the only therapeutic option, and stem cell transplantation the only curative treatment for severe anemias. Unfortunately, a lack of immune-matched cells often hampers these therapies.

The TRACER consortium works on studying disease mechanisms as well as the production of mature bloodcells/HSCs from gene-corrected induced pluripotent stem-cells for therapeutic purposes. The team at TU Delft will focus on development of bioreactor technology for reliable high-density, low cost stem cell production for blood transfusion and curative applications. The team will consist of two PhD students, of which the current vacancy focuses on process modeling and simulation, whereas the prospective colleague will work on experimental cultivation and process monitoring/control. Within this project, you will actively work together with all partners, particularly Dutch blood bank Sanquin and Getinge-Applikon for bioreactor/process development.

PhD Project description:

The main objective of the process simulation project is to gain detailed insights in the cultivation environment, particularly conisdering gas-to-liquid mass transfer, mixing, hydrodynamic stresses and agglomeration using computational fluid dynamics.

Key focus points:

• Provide mechanistic insights into experimental observations related to HSC cultivation.
• Study integration of cellular response models with hydrodynamic models for cell culture applications.
• Provide input for experimental design choices.
• Design of robust cultivation protocols at various scales, from shake flask to fermentor, eventually leading to a production protocol for the manufacturing of blood cells/HSCs for therapeutic applications.

Several reactor configurations and scales, from shakeflask to production reactor, will be considered. The obtained insights will be use to further push the limits of the cultivation to obtaining higher cell numbers per unit volume. The CFD simulations will be used to inform process monitoring and control strategies. Insights obtained from the experimental work (ideally, including metabolic/proteomic models) will be included in the simulations. Additionally, there is room to explore the combination of hybrid mechanistic/data-driven modeling in the scope of bioprocess modeling.

Research group:

The project will take place in the Process simulation & Hydrodynamics group of the section Bioprocess Engineering at the department of Biotechnology. Our main objective is to study bioprocesses from the cellular point of view; how can we study interaction between cells and their environment, how does this affect process performance and how can we use the acquired knowledge to design better bioprocesses?

We are looking for a candidate that is self-driving and that can act as the manager of their own project. A strong background in process technology and an affinity for process simulation is desired. Considering the broad, multi-disciplinary nature of the consortium, we are looking for candidates that can effectively communicate their methods and results to stakeholders of various backgrounds, including non-technical.

• The ideal candidate holds an MSc (or equivalent) degree in biochemical engineering, chemical engineering, applied physics or a comparable program.
• A good academic track record is required, particularly in courses related to (bio)process engineering, transport phenomena and numerical techniques.
• Affinity for numerical analysis is necessary.
• Programming experience is strongly desired, ideally in Python or Julia.
• Experience with biomedical processes and (mammalian/human) cell biology is an advantage, but not essential.
• Fluent in English (written and spoken)
• Excellent communication skills and presentation capabilities, including communication with non-technical stakeholders. 

Doing a PhD at TU Delft requires English proficiency at a certain level to ensure that the candidate is able to communicate and interact well, participate in English-taught Doctoral Education courses, and write scientific articles and a final thesis. For more details please check the Graduate Schools Admission Requirements .

Doctoral candidates will be offered a 4-year period of employment in principle, but in the form of 2 employment contracts. An initial 1,5 year contract with an official go/no go progress assessment within 15 months. Followed by an additional contract for the remaining 2,5 years assuming everything goes well and performance requirements are met.

Salary and benefits are in accordance with the Collective Labour Agreement for Dutch Universities, increasing from € 2443 per month in the first year to € 3122 in the fourth year. As a PhD candidate you will be enrolled in the TU Delft Graduate School. The TU Delft Graduate School provides an inspiring research environment with an excellent team of supervisors, academic staff and a mentor. The Doctoral Education Programme is aimed at developing your transferable, discipline-related and research skills.

The TU Delft offers a customisable compensation package, discounts on health insurance and sport memberships, and a monthly work costs contribution. Flexible work schedules can be arranged. For international applicants we offer the Coming to Delft Service and Partner Career Advice to assist you with your relocation.

Delft University of Technology is built on strong foundations. As creators of the world-famous Dutch waterworks and pioneers in biotech, TU Delft is a top international university combining science, engineering and design. It delivers world class results in education, research and innovation to address challenges in the areas of energy, climate, mobility, health and digital society. For generations, our engineers have proven to be entrepreneurial problem-solvers, both in business and in a social context. At TU Delft we embrace diversity and aim to be as inclusive as possible (see our Code of Conduct ). Together, we imagine, invent and create solutions using technology to have a positive impact on a global scale.

Challenge. Change. Impact! 

With more than 1,000 employees, including 135 pioneering principal investigators, as well as a population of about 3,400 passionate students, the Faculty of Applied Sciences is an inspiring scientific ecosystem. Focusing on key enabling technologies, such as quantum- and nanotechnology, photonics, biotechnology, synthetic biology and materials for energy storage and conversion, our faculty aims to provide solutions to important problems of the 21st century. To that end, we train students in broad Bachelor's and specialist Master's programmes with a strong research component. Our scientists conduct ground-breaking fundamental and applied research in the fields of Life and Health Science & Technology, Nanoscience, Chemical Engineering, Radiation Science & Technology, and Engineering Physics. We are also training the next generation of high school teachers and science communicators.

Click here to go to the website of the Faculty of Applied Sciences.

Department of Biotechnology

Innovation is crucial to fulfil the potential of industrial biotechnology for sustainable production of fuels, chemicals, materials, food and feed. Similarly, scientific and technological advances in environmental biotechnology are needed to enable novel approaches to water purification, and ‘waste-to-product’ processes thus contributing to a circular economy. Increased fundamental knowledge encompassing enzymes, microorganisms and processes are essential for progress in this field. The Department of Biotechnology covers this research area and, based on new insights, selects, designs and tests new biobased catalysts, micro-organisms, and processes.

The position is available in the section Bioprocess Engineering

Are you interested in this vacancy? Please apply before 25 June 2022 via the application button and upload only your motivation letter and CV.

• A pre-employment screening can be part of the selection procedure.
• Applying for an exemption for specific research and educational areas is an obligatory part of the selection procedure for this vacancy. This exemption must be obtained from the Ministry of Education, Culture and Science (OCW) before an employment contract is agreed upon. Click here for more information.
• You can apply online. We will not process applications sent by email and/or post.
• Acquisition in response to this vacancy is not appreciated.

Only for more information about this vacancy, please contact Dr. ir. Cees Haringa, Assistant Professor Bioprocess Engineering, per e-mail [email protected]

Only for more information about the application procedure, please contact Ms. Kawieta Ramautar, Management Assistant, per e-mail [email protected]

* It is our aim to have the interviews in July 5, 8 or 12 and to fulfil the position preferably in August or September 2022.