PhD position on the fundamentals of microfluidic lipid nanoparticle formation – University of Twente – Enschede

1 september 2024 0

University of Twente

You will be part of the highly multidisciplinary consortium NANOSPRESSO-NL (8 M€). We aim to study, develop, and implement a disruptive technology for decentralized and small-scale bedside production of high quality and affordable nucleic acid nanomedicines for the treatment of orphan (rare) diseases. The technology is based on the microfluidic formation of lipid nanoparticles (LNPs) that carry nucleic acid therapeutics such as mRNA. The microfluidic formation of LNPs is achieved when a stream of lipids (surfactants) dissolved in ethanol is mixed with water such that the solubility of the lipids decreases below a critical threshold at which the lipids and therapeutics phase separate and self-assemble into LNPs (~100 nm diameter). This is very similar but much more complex to a famous fluid dynamical problem: The Ouzo (Greek alcoholic drink) effect where nano- and microdroplets of oil nucleate when the Ouzo is diluted with water. Your task within this project is to unravel the coupling between the fluid mechanics of the convective and diffusive mixing and the physicochemistry of the self-assembly of the lipid and therapeutic molecules. You will thus work on the fundamentals of LNP formation with the ultimate aim to develop understanding required to allow bottom-up design of microfluidic devices and operating conditions tailored to specific needs in terms of LNP size distribution and therapeutic loading. To gain understanding, you will design and fabricate microfluidic chips and you will be trained to master a broad range of experimental techniques including ultra-high-speed (fluorescence) imaging at the sub-µs timescale and confocal imaging. Whenever possible, you will develop hand in hand with the experiments accompanying numerical simulations and theory to test our understanding.

The NANOSPRESSO-NL consortium works on all aspects of brining personalized LNP therapeutics to the clinic starting at understanding the microfluidic formation of LNPs (you), the development of novel microfluidic devices (you), the implementation of the microfluidic devices in a cartridge containing all fluids (analogous to a Nespresso cup), the development of a tabletop device that can operate the cartridge (Nespresso coffee machine), cell and preclinical experiments, to all legislation related to bringing new medicine to the market. This is thus a unique opportunity to develop deep fundamental physicochemical (hydrodynamic) understanding of LNP self-assembly with the possibility to achieve a relatively short-term impact while gaining insight in all aspects that play a role in the development of new pharmaceutical products.

You will be embedded in the dynamic BIOS/Lab on a Chip group, which is part of the Max Planck Center Twente for Complex Fluid Dynamics, the J.M. Burgers Research Center for Fluid Mechanics (JMBC), and the MESA+ Institute for Nanotechnology. You will closely collaborate with the Laboratory for Clinical Chemistry & Hematology of the University Medical Center Utrecht (Prof. Dr. Raymond Schiffelers), with SINTEF in Trondheim (Norway), as well as with a pharmaceutical spin off company of the UT (Solstice Pharmaceuticals). Your direct colleagues in the BIOS group are active and organize many after-work activities.

Your profile

  • You have a strong background in physical chemistry, (applied) physics, chemical engineering, biomedical engineering, or in a closely related discipline. 
  • You are enthusiastic and highly motivated to do a PhD and are driven by curiosity.
  • You have strong communication skills, including fluency in written and spoken English and you like to collaborate within a highly multidisciplinary team.
  • You have experimental experience and are creative in the lab.
  • Knowledge on fluid mechanics, microfluidics, microscopy, experience in image and data analysis, and/or in physical chemistry are a plus.

    • Our offer

  • As a PhD candidate at UT, you will be appointed to a full-time position for four years, with a qualifier in the first year, within a very stimulating and exciting scientific environment;
  • The University offers a dynamic ecosystem with enthusiastic colleagues;
  • Your salary and associated conditions are in accordance with the collective labour agreement for Dutch universities (CAO-NU);
  • You will receive a gross monthly salary ranging from € 2.770,- (first year) to € 3.539,- (fourth year);
  • There are excellent benefits including a holiday allowance of 8% of the gross annual salary, an end-of-year bonus of 8.3%, and a solid pension scheme;
  • The flexibility to work (partially) from home;
  • A minimum of 232 leave hours in case of full-time employment based on a formal workweek of 38 hours. A full-time employment in practice means 40 hours a week, therefore resulting in 96 extra leave hours on an annual basis.
  • Free access to sports facilities on campus
  • A family-friendly institution that offers parental leave (both paid and unpaid);
  • You will have a training programme as part of the Twente Graduate School where you and your supervisors will determine a plan for a suitable education and supervision;
  • We encourage a high degree of responsibility and independence, while collaborating with close colleagues, researchers and other staff.

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