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Generation of a Human iPSC-Based Blood-Brain Barrier Chip
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Multiplexed blood-brain barrier organ-on-chip.

M Zakharova1, M A Palma do Carmo1, M W van der Helm1

  • 1BIOS Lab on a Chip group, MESA+ Institute for Nanotechnology, Technical Medical Centre, Max Planck Institute for Complex Fluid Dynamics, University of Twente, The Netherlands. m.zakharova@utwente.nl.

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|August 7, 2020
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Summary

This study introduces a novel multiplexed organ-on-chip device enabling parallel testing of eight experimental conditions. This polydimethylsiloxane (PDMS) chip enhances reproducibility for drug testing and biomedical research.

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Area of Science:

  • Biomedical Engineering
  • Microfluidics
  • Tissue Engineering

Background:

  • Organ-on-chip (OOC) models are crucial for pharmaceutical and biomedical research.
  • Existing OOC models often lack the capacity for parallel testing of multiple stimuli, limiting experimental throughput and reproducibility.

Purpose of the Study:

  • To develop a multiplexed polydimethylsiloxane (PDMS) organ-on-chip device capable of simultaneously addressing eight parallel channels.
  • To enable parallel testing of different experimental conditions and facilitate real-time cell culture monitoring.

Main Methods:

  • Fabrication of a multiplexed PDMS chip with eight parallel channels and eight individual outlets using soft lithography.
  • Assembly of a two-layer device with a transparent PDMS membrane featuring through-hole pores for visual inspection.
  • Recapitulation of the blood-brain barrier model using human cerebral microvascular endothelial cells (hCMEC/D3) and human astrocytes.

Main Results:

  • Successful culture of endothelial cells and astrocytes, confirmed by immunostaining for tight junction ZO-1, adherence junction VE-cadherin, and glial fibrillary acidic protein (GFAP).
  • Demonstrated multiplexed permeability studies showing differential passage of FITC-dextran molecules (4 kDa and 20 kDa) across the cellular barrier.
  • Validated the device's functionality in recapitulating a functional blood-brain barrier model.

Conclusions:

  • The developed multiplexed organ-on-chip device significantly enhances experimental throughput and reproducibility.
  • The device is suitable for parallel drug testing and serves as a valuable tool for studying barrier tissue functions.
  • This technology holds promise for advancing pharmaceutical screening and personalized medicine applications.