Join our research team and embark on a multidisciplinary PhD journey on experimental bio microfluidics with a high-impact application in health: molecular imaging and drug delivery with (targeted) microbubbles and ultrasound [1]. We search for a highly motivated candidate with strong hands on and creative experimental skills. In this project, you will work on cell culture in organ on-chip devices, ultra-high-speed (fluorescence) microscopy imaging, confocal imaging, pulsed ultrasound (imaging), trans-endothelial electrical resistance measurements, and the production of novel functionalized (targeted and drug-loaded) microbubbles using microfluidic flow focusing devices. While the primary focus of the project is on experiments, you can also work on theory, modelling, and simulations.

The aim of the project is to understand the interaction between ultrasound-driven microbubbles and (artificial) tissue and to thereby design new monodisperse microbubble agents for molecular imaging and drug delivery. You will use organ on-chip systems as artificial tissues [2]. The microbubbles of interest are coated with a monolayer of phospholipids, which stabilizes the bubbles against dissolution. Additionally, the shell can be decorated with (i) targeting molecules that specifically bind to diseased tissue and (ii) drugs loaded in for example liposomes. Using ultrasound, the bubbles can be spatially detected based on the strong echo that these bubble produce when they are excited by ultrasound. The strong bubble echo originates from ultrasound-driven volumetric bubble oscillations. There are strong indications that the echo of a molecularly bound bubble is different from a non-bound bubble, which demonstrates a large potential for molecular ultrasound imaging: the acoustic discrimination of bound versus non-bound bubbles [3]. Volumetric microbubble oscillations do not only facilitate bubble echo-localization, but they can also be used to perform mechanical action on nearby tissue and thereby transiently disrupt biological barriers (e.g., the blood-brain barrier) for drug delivery. Drugs attached to or incorporated on the bubble shell can then be locally delivered by vigorously driving the bubble with ultrasound. Thus, microbubbles have a huge potential for medical applications. However, their ultrasound-driven response depends on their size, coating properties, and potentially binding characteristics, which remain currently uncontrolled thereby complicating clinical translation [4]. Besides a lack of control on bubble characteristics, there’s a lack of understanding on bubble – tissue interaction. This project aims to contribute to both gaps by gaining control to gain understanding and by gaining understanding to gain control.

In this project, you are encouraged to follow a novel approach that is completely based on microfluidics. You will use microfluidic flow focusing devices to produce your own targeted (drug-loaded) microbubbles with a specific monodisperse size, shell properties, and binding characteristics [5]. You will characterize the MHz oscillation behaviour of your bubbles using ultra-high-speed imaging at 10 million frames per second and by recording their acoustic attenuation and echo in organ on-chip devices that you will design and develop yourself in close collaboration with experts on microfluidics and cell biology [2]. To measure the biological response of the model tissue in response to the oscillating bubbles, you will employ trans-endothelial electrical resistance measurements, fluorescence imaging of model drug diffusion, and immunohistology (confocal fluorescence imaging). Additionally, you will closely collaborate with a postdoc working in the same project on the localization and acoustic discrimination of your bound versus non-bound bubbles using a preclinical ultrasound scanner.

You will work in a dynamic team of 5 PhD students and 3 postdocs all working on microbubbles, droplets, and vesicles for (ultrasound) diagnostics and therapy. In your PhD journey, you have a unique toolbox with facilities including ultra-high-speed (fluorescence) imaging, high-power lasers, stroboscopic laser induced fluorescence imaging, confocal imaging, and cleanroom fabrication. You will be embedded in the BIOS/Lab on a Chip group, which is part of the Max Planck Centre Twente for Complex Fluid Dynamics, the J.M. Burgers Research Centre for Fluid Mechanics (JMBC), and the MESA+ Institute for Nanotechnology. As such, you are surrounded by world-leading scientists on all aspects of the project, with whom you are encouraged to collaborate. You are also encouraged to follow additional training in relevant courses and training programs, and to visit conferences and summer/winter schools on relevant topics. Your direct colleagues are friendly and active; they organize many after-work activities.

[1] E. Stride et al. "Microbubble agents: New directions." Ultrasound in medicine & biology 46.6 (2020): 1326-1343.

[2] M.W. van Der Helm et al. "Microfluidic organ-on-chip technology for blood-brain barrier research." Tissue barriers 4.1 (2016): e1142493.

[3] B. Dollet, P. Marmottant, and V. Garbin. “Bubble dynamics in soft and biological matter.” Annual Review of Fluid Mechanics 51 (2019), 331-355.

[4] B. van Elburg et al. "Dependence of sonoporation efficiency on microbubble size: An in vitro monodisperse microbubble study." Journal of Controlled Release 363 (2023): 747-755.

[5] T. Segers et al. "Stability of monodisperse phospholipid-coated microbubbles formed by flow-focusing at high production rates." Langmuir 32.16 (2016): 3937-3944.

• You have a strong background in biomedical engineering, (applied) physics, mechanical engineering, chemical engineering, or in a closely related discipline.
• You are enthusiastic and highly motivated to do a PhD and are driven by curiosity.
• You have a technical background with experimental experience in cell culture and are creative in the lab.
• Knowledge on cell culture, fluid mechanics, microfluidics, microscopy, optics, and experience in image and data analysis are a plus.
• You have strong communication skills, including fluency in written and spoken English.
• You are able to start the PhD position (remotely) by May 8th latest.

• We want you to play a key role in an ambitious project in an inspiring and stimulating international work environment.
• We provide excellent mentorship and a stimulating, modern research environment with world-class research facilities (cleanroom, ultra-high-speed cameras, lasers, etc).
• You will be embedded in a dynamic research group with colleagues working on similar topics.
• Additionally, the University of Twente is a green campus with excellent facilities and resources for professional and personal development and offers a wide variety of sports facilities.
• You will follow a high-quality personalized educational program.
• The research will result in a PhD thesis at the end of the employment period.
• You will have an employment contract for the duration of 4 years with 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.
• We strive for diversity and fairness in hiring.