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Developing a Blood-Brain Barrier On-Chip for Microbubble Assisted and Focus Ultrasound Induced Permeabilization Studies

Tammes, Lieke (2024) Developing a Blood-Brain Barrier On-Chip for Microbubble Assisted and Focus Ultrasound Induced Permeabilization Studies.

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Abstract:This study investigates the issues related to cell culture stability and monolayer formation in microfluidic chips for microbubble-assisted focused-ultrasound induced blood-brain barrier permeabilization. Current research is exploring microbubble-assisted focused-ultrasound to locally and non-invasively permeabilize the blood-brain barrier, using an in vitro blood-brain-barrier-on-chip model. To solve the reproducibility issues this model-on-chip has, this report has designed a new chip, meant to be used with applied flow. The new chip design will allow live cell imaging and for this purpose accommodate an objective lens between the pipette points for precise imaging. Calculations determined that the resulting shear stress on the cells was 1.98 dyne/cm2, which is in the range of physiological shear stress. The chip fabrication process involved creating molds using micromilling, SU-8 clean room fabrication, and 3D-printing, with the SU-8 mold proving to be most suitable for making chip with the desired qualities. Chips were prepared by pouring a PDMS mixture over the mold, curing it, and bonding the membrane to the chip parts after oxygen plasma treatment. Cell culture experiments used induced pluripotent stem cells differentiated into endothelial cells, seeded into the chips and subsequently incubated, with flow applied to some chips to study its effects. The first two experiments had a low cell survival rate and the third experiment showed a diminishing of cell confluency over time. Analysis using microscopy and ImageJ revealed variability in cell monolayer confluence. It is suggested that this variability could be due to surface hydrophobicity or the delicate nature of induced pluripotent stem cells. It is recommended to repeat the research, focussing on only one aspect at a time.
Item Type:Essay (Bachelor)
Faculty:TNW: Science and Technology
Subject:42 biology
Programme:Biomedical Technology BSc (56226)
Link to this item:https://purl.utwente.nl/essays/104807
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