Fabrication and Applications of Three Dimensional Porous Microwells
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Fabrication and Applications of Three Dimensional Porous Microwells Christina L. Randall,1 Yevgeniy V. Kalinin,2 Anum Azam,1 David H. Gracias 2,3 1 Department of Biomedical Engineering, 2Department of Chemical and Biomolecular Engineering and 3Department of Chemistry, Johns Hopkins University, 3400 N Charles Street Baltimore, MD 21218, USA. ABSTRACT In many biological applications, such as cell therapy and drug delivery, there is a need to enhance diffusion by enabling chemical transport in all three dimensions. We highlight this need by comparing diffusion in a conventional two-dimensional (2D) microwell with diffusion in a three-dimensional (3D) cubic microwell using numerical simulations. We also describe the fabrication of hollow polymeric (and biocompatible) cubic microwells and microwell arrays. We emphasize that since the assembly process is compatible with 2D lithographic patterning, porosity can be precisely patterned in all three dimensions. Hence, this platform provides considerable versatility for a variety of applications. INTRODUCTION Our concept of a 3D microwell has been described previously [1-2]. As compared to traditional 2D microwells, polyhedra with precisely patterned sidewalls can function as miniaturized analogs, but feature diffusion in all three dimensions. All 3D polyhedral microwells were created using a self-folding strategy that has previously been shown to work across length scales from 100 nm to 2 mm [3-6], with a range of materials including metals, dielectrics and now polymers. The main advantage of having a 3D microwell over a conventional 2D microwell is that interaction of encapsulated contents with the surroundings is enhanced in all three dimensions. Here, we first describe the need for such microwells by comparing diffusion in traditional microwells, which are typically accessible only from one face, and our 3D devices, that feature porosity in all three dimensions. We then describe the creation of polymeric microwells by self-folding. Polymeric microwells are especially advantageous since they are transparent and can be fabricated with biocompatible materials. Finally, we explore the creation of 3D microwell arrays that provide truer analogs of 2D microwell geometries but feature enhanced diffusion in all three dimensions. METHODS Numerical Simulations Three-dimensional numerical models were built in COMSOL Multiphysics 3.5 (COMSOL, Inc., Burlington, MA) and then numerical solutions were sought for the diffusion equation [7]. We assumed that a sample of living tissue 10 μm in size was placed at the geometrical center of the microwell. We also assumed that this tissue consumed all oxygen in its immediate vicinity and that the medium outside of microwells was well mixed. Accordingly, oxygen concentration outside of the microwell was always equal to oxygen concentration in the bulk.
Fabrication of polymeric microwells featuring porosity in all three dimensions Microwells were fabricated using SU-8 for the panels and poly(ε-caprolactone) (PCL) for the hinges. SU-8
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