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bioRxiv · 10.64898/2026.06.21.733618

NeuroEnergetics-on-Chip: a novel 3-compartment microfluidic platform to study metabolic interactions between brain parenchyma and cerebral vasculature

Ceballos Torres, A. P.·Montesi, L.·Loel, L.·Yanovska, M.·Venckute, J.·Jessika, J.·Wu, T.·Benito Zarza, L.·Cognetti, J.·Fotouhi, O.·Klavins, K.·Ygberg, S.·Wredenberg, A.·Wedell, A.·Herland, A.·Rogal, J.
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Abstract

Neurological disorders are a major cause of death and disability worldwide. The brains energy metabolism is essential to its proper function, yet the mechanisms driving neuroenergetic dysfunction remain poorly understood. A key challenge is the limited availability of human-relevant models that can reproduce the complexity of brain physiology. An Organ-on-Chip (OoC) system was developed to mimic the neurovascular unit metabolic coupling by incorporating human isogenic iPSC-derived endothelial-like cells, pericyte-like cells, astrocytes, and a cerebral organoid, representing the main cellular components of the NVU. The novel, customized microfluidic platform enables research on neurovascular coupling by interconnecting a blood-brain barrier-on-a-chip model with a 3D brain parenchymal compartment to mimic physiological conditions. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=182 SRC="FIGDIR/small/733618v1_ufig1.gif" ALT="Figure 1"> View larger version (75K): org.highwire.dtl.DTLVardef@9fc9f3org.highwire.dtl.DTLVardef@838a7corg.highwire.dtl.DTLVardef@1f8df76org.highwire.dtl.DTLVardef@16ef40_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Ceballos Torres, A. P., Montesi, L., Loel, L., Yanovska, M., Venckute, J., Jessika, J., Wu, T., Benito Zarza, L., Cognetti, J., Fotouhi, O., Klavins, K., Ygberg, S., Wredenberg, A., Wedell, A., Herland, A., Rogal, J.. 2026-06-25. NeuroEnergetics-on-Chip: a novel 3-compartment microfluidic platform to study metabolic interactions between brain parenchyma and cerebral vasculature. https://doi.org/10.64898/2026.06.21.733618

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