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Title: A reversibly sealed, easy access, modular (SEAM) microfluidic architecture to establish in vitro tissue interfaces

Microfluidic barrier tissue models have emerged as advanced in vitro tools to explore interactions with external stimuli such as drug candidates, pathogens, or toxins. However, the procedures required to establish and maintain these systems can be challenging to implement for end users, particularly those without significant in-house engineering expertise. Here we present a module-based approach that provides an easy-to-use workflow to establish, maintain, and analyze microscale tissue constructs. Our approach begins with a removable culture insert that is magnetically coupled, decoupled, and transferred between standalone, prefabricated microfluidic modules for simplified cell seeding, culture, and downstream analysis. The modular approach allows several options for perfusion including standard syringe pumps or integration with a self-contained gravity-fed module for simple cell maintenance. As proof of concept, we establish a culture of primary human microvascular endothelial cells (HMVEC) and report combined surface protein imaging and gene expression after controlled apical stimulation with the bacterial endotoxin lipopolysaccharide (LPS). We also demonstrate the feasibility of incorporating hydrated biomaterial interfaces into the microfluidic architecture by integrating an ultra-thin (< 1 μm), self-assembled hyaluronic acid/peptide amphiphile culture membrane with brain-specific Young’s modulus (~ 1kPa). To highlight the importance of including biomimetic interfaces into microscale models we report multi-tieredmore » readouts from primary rat cortical cells cultured on the self-assembled membrane and compare a panel of mRNA targets with primary brain tissue signatures. As a result, we anticipate that the modular approach and simplified operational workflows presented here will enable a wide range of research groups to incorporate microfluidic barrier tissue models into their work.« less
 [1] ;  [2] ;  [2] ;  [2] ;  [3]
  1. Sandia National Lab. (SNL-CA), Livermore, CA (United States); Univ. of Texas at Arlington Research Institute, Fort Worth, TX (United States)
  2. Sandia National Lab. (SNL-CA), Livermore, CA (United States)
  3. Univ. of Illinois at Chicago, Chicago, IL (United States)
Publication Date:
Grant/Contract Number:
10027IA-3167; AC04-94AL85000
Published Article
Journal Name:
Additional Journal Information:
Journal Volume: 11; Journal Issue: 5; Journal ID: ISSN 1932-6203
Public Library of Science
Research Org:
Sandia National Lab. (SNL-CA), Livermore, CA (United States); Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)
Sponsoring Org:
Country of Publication:
United States
microfluidics; RNA extraction; gene expression; lasers; cell cultures; fluidics; RNA isolation; membrane staining
OSTI Identifier:
Alternate Identifier(s):
OSTI ID: 1266214