Fabrication of free standing microporous COC membranes optimized for in vitro barrier tissue models

This paper reports a low-cost method for micro fabrication of cyclic olefin copolymer (COC) membranes with optimized thickness and pore size for creation of in vitro tissue models. The method is capable of creating membranes satisfying the technical requirement of in vitro barrier tissue models on microfluidic chips such as small thickness, customizable pore size and pore density, and low auto fluorescence. Micro pore arrays with pore diameter of 3-5 pm were created on membranes with 1-2 pm thickness with free standing area of more than 3 mm2. The method is based on spin coating of a polymer bilayer and hot embossing. First polyvinyl alcohol (PVA) is coated as a sacrificial layer and then COC polymer film is formed on PVA layer. The hot embossing process with a micro fabricated silicon master created indentations on the COC film. A brief oxygen plasma treatment after hot embossing eliminated the residual film in the indentations. The plasma treatment created smooth round shaped holes in the indented area. The membrane was released by dissolving the sacrificial PVA layer in water. The method is highly reproducible and simple indicating its compatibility for fabrication of disposable membranes. We also integrated the membrane in a microfluidic device to test the performance of the membrane as a support layer for cells during in vitro barrier tissue experiments. The experiments conducted with fibroblasts and endothelial cells indicated that the membrane successfully supports cell attachment and proliferation. We conclude that this fabrication method should be a useful tool to create low-cost disposable microporous membrane components for in vitro barrier tissue model systems on microfluidic chips. (C) 2013 Published by Elsevier B.V.