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Rapid Prototyping of Multilayer Microphysiological Systems.

Sanjin Hosic1, Adam J Bindas1, Marissa L Puzan1

  • 1Department of Chemical Engineering, Northeastern University, 360 Huntington Ave., 313 Snell Engineering, Boston, Massachusetts 02115, United States.

ACS Biomaterials Science & Engineering
|July 19, 2021
PubMed
Summary
This summary is machine-generated.

We developed a rapid, economical method for fabricating thermoplastic organs-on-chips without poly(dimethylsiloxane) (PDMS). This new technique enables faster cell differentiation and supports complex co-cultures for advanced in vitro modeling.

Keywords:
adhesiveeconomicalfabricationgut chipintestinal organoidorgan-on-chippatient-derived cellsprimary epitheliumthermoplastic

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Area of Science:

  • Biotechnology
  • Tissue Engineering
  • Microfluidics

Background:

  • Traditional 2D cell cultures lack biorelevance.
  • Poly(dimethylsiloxane) (PDMS) soft lithography for organs-on-chips has limitations in prototyping time and cost.
  • There is a need for more accessible and efficient methods to create advanced in vitro models.

Purpose of the Study:

  • To develop a novel, cost-effective, and rapid fabrication method for multilayered thermoplastic organs-on-chips.
  • To demonstrate the biocompatibility and functionality of these PDMS-free chips for cell culture.
  • To showcase the potential for creating complex multicellular tissue models.

Main Methods:

  • Laser cutting and assembly of thermoplastic materials using double-sided adhesives.
  • Fabrication of PDMS-free, Luer-compatible microfluidic devices.
  • Culturing Caco-2 cells and primary human small intestinal organoids on the chips.
  • Co-culturing differentiated monolayers and 3D organoids in a trilayer chip configuration.

Main Results:

  • Economical prototyping ($2 per chip) and rapid parallel fabrication (within hours).
  • Demonstrated biocompatibility with epithelial cells and organoids, forming confluent monolayers with tight junctions and low permeability.
  • Achieved significantly faster Caco-2 cell differentiation (∼4x) with increased mucus production compared to controls.
  • Successfully fabricated and demonstrated a complex trilayer chip for co-culturing 2D and 3D human tissues, maintaining tissue structure and stem cell proliferation for 10 days.

Conclusions:

  • The cut-and-assemble method provides a rapid and economical approach for manufacturing microfluidic organs-on-chips.
  • This PDMS-free technique overcomes limitations of traditional lithography, enabling diverse chip geometries.
  • The developed organs-on-chips are suitable for studying complex multicellular tissues and advancing in vitro modeling.