Simulation of in-vivo-equivalent epithelial barriers using a micro fluidic device

Biomed Microdevices. 2014 Apr;16(2):191-8. doi: 10.1007/s10544-013-9821-5.

Abstract

In biomedical approaches cell culture models do often not fully represent their biological counterparts. Often the methods used do not completely mimic the in-vivo situation, either by using only single-cell-type culture approaches, or by using inadequate culture conditions. We therefore developed a variable system based on individual modules to simulate in vitro equivalent cell-barriers (e.g. for mucous layers). This system allows the growth of different communicating cell types in micro channels. Hot embossing is used to fabricate the micro structured polymer sheets. The stamp for hot embossing is fabricated by UV-lithography/electroforming or by micro milling. The system consists of a container with micro fluidic modules and a pump-system for a continuous medium-supply. An individual module is made of two micro-structured polycarbonate-sheets separated by a transmissible polycarbonate membrane. The two sheets are arranged orthogonally to induce a cross flow. The system is highly variable by channel-geometry (height and width), capacity (number of micro fluidic modules), and pore sizes of the transmissible membranes. In a first approach we simulated the intestinal mucosa. Epithelial cells and primary neurons of the enteric nervous system were cultured on both sides of the transmissible membrane within the two different compartments. So the cells could be supplied with two different media. We kept a mono-culture of primary neurons or epithelial cells for 5 days and a co-culture between these two cell-types was established for 4 days. The proposed system delivers a sophisticated model for the simulation of various epithelial layers which takes the specific biological properties into account.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Coculture Techniques / instrumentation*
  • Coculture Techniques / methods
  • Intestinal Mucosa / cytology*
  • Intestinal Mucosa / metabolism
  • Microfluidic Analytical Techniques / instrumentation*
  • Microfluidic Analytical Techniques / methods
  • Neurons / cytology*
  • Neurons / metabolism
  • Primary Cell Culture / instrumentation*
  • Primary Cell Culture / methods
  • Rats