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The Baby Blood-Brain Barrier Chip

Background

Jaundice occurs in 60-80% of all newborns. This complication is related to yellow discoloration of the skin, due to elevated blood and skin concentrations of the yellow molecule bilirubin. Mild jaundice is harmless, but in case of severe jaundice, bilirubin diffuses into the brain. This causes irreversible brain damage (kernicterus) and in worse cases death. Therefore, current medical practice adheres to close monitoring of bilirubin concentrations in blood (TSB) – requiring up to three harmful samples per day. Disturbingly, some newborns still develop kernicterus even though the TSB is well below the safety limits.

Could it be that the TSB is not the only determinant of how much bilirubin ends up in the brain? Alternative explanations may be (a) lack of clearance from the brain, or (b) increased extravasation due to brain capillary damage or dysfunction. These alternative hypotheses can be tested by using a laboratory model of the newborn brain vasculature: a ‘baby blood-brain barrier (BBB) on a chip’.

The BBB-on-chip is a microfluidic model of a blood vessel in the human brain. It contains two microfluidic compartments – one representing the blood, and one representing the brain – separated by a porous membrane. By culturing human brain endothelium on the membrane, a living, microengineered model of the human brain vasculature is established.

Aim

In this project you will model a newborn BBB on a chip. Using this model, you will investigate the relation between the TSB and the brain bilirubin concentration.

Content

In this project, you will:

1.

Adjust the existing BBB-on-chip model to a newborn BBB on a chip.

2.

Control the TSB and other important factors, such as systemic and local inflammatory factors, inside the model, and monitor the extravasation and clearance of bilirubin in the brain compartment of the chip.

3.

Quantify the relation between the TSB and the brain bilirubin concentration.

Contact

For more information, please contact Nienke Bosschaart (n.bosschaart@utwente.nl), Andries van der Meer (andries.vandermeer@utwente.nl), or Loes Segerink (l.i.segerink@utwente.nl).